Described and featured are compositions, a system and methods for identifying and selecting substrates of E3 ligases by ubiquitin biotinylation. The components of the compositions, system and methods are ubiquitin- and interaction-specific, thereby providing the enrichment and identification of endogenous or exogenous E3 ligase substrate molecules that are proximally ubiquitinated and biotinylated by components designed to interact both physically and functionally in the compositions, system and methods. The compositions, system and methods are useful and advantageous for identifying and selecting E3 ligase substrates (and/or associated molecules) that are modulated or induced by other agents, such as immunomodulatory imide agents (IMiDs), molecular glues and bifunctional proteolysis targeting chimeras (PROTAC®s).
C12Q 1/48 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismesCompositions à cet effetProcédés pour préparer ces compositions faisant intervenir une transférase
C12N 9/00 - Enzymes, p. ex. ligases (6.)ProenzymesCompositions les contenantProcédés pour préparer, activer, inhiber, séparer ou purifier des enzymes
2.
COMPOSITIONS AND METHODS FOR EFFICIENT IN VIVO DELIVERY
Disclosed herein are compositions, methods, kits, and systems relating to efficient delivery of cargos (e.g., therapeutic cargos) into cells, for instance, for in vivo delivery. The present disclosure provides lipid-containing particles (e.g., virus-like particles) for delivering therapeutic cargos. The present disclosure also provides polynucleotides encoding the lipid-containing particles provided herein, which may be useful for producing said lipid-containing particles. Also provided are methods for editing nucleic acid molecules in cells using the lipid-containing particles provided herein, as well as cells and kits comprising the lipid-containing particles.
E. faecalisE. faecalis phage-derived antimicrobial agent (efagins). The invention also features compositions and methods of using the efagins to treat bacterial infections.
C12Q 1/689 - Produits d’acides nucléiques utilisés dans l’analyse d’acides nucléiques, p. ex. amorces ou sondes pour la détection ou l’identification d’organismes pour les bactéries
C12Q 1/6806 - Préparation d’acides nucléiques pour analyse, p. ex. pour test de réaction en chaîne par polymérase [PCR]
C12Q 1/6837 - Couplage enzymatique ou biochimique d’acides nucléiques à une phase solide utilisant des réseaux de sondes ou des puces à sondes
G16B 25/20 - Réaction en chaîne par polyméraseConception d’amorces ou de sondesOptimisation de la sonde
5.
METHODS AND COMPOSITIONS FOR DETERMINING THE ANTIGEN SPECIFICITY OF T CELLS
The present disclosure provides methods and compositions for determining the antigen specificity of T cells and in a scalable, high-throughput approach. The disclosure provides methods for producing RNA-barcoded pMHC multimers that can be decoded using single-cell RNA sequencing methods. Among these, disclosed herein are multivalent virus-like-particles bound with pMHC in E. coli cells that encapsulate an RNA barcode encoding the peptide identity.
C12Q 1/6881 - Produits d’acides nucléiques utilisés dans l’analyse d’acides nucléiques, p. ex. amorces ou sondes pour le typage de tissu ou de cellule, p. ex. sondes d’antigène leucocytaire humain [HLA]
C07K 1/22 - Chromatographie d'affinité ou techniques analogues basées sur des procédés d'absorption sélective
C07K 14/195 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant de bactéries
Disclosed herein are compositions, methods, kits, and systems relating to efficient delivery of cargos (e.g., therapeutic cargos) into cells, for instance, for in vivo delivery. The present disclosure provides lipid-containing particles (e.g., virus-like particles) for delivering therapeutic cargos. The present disclosure also provides polynucleotides encoding the lipid-containing particles provided herein, which may be useful for producing said lipid-containing particles. Also provided are methods for editing nucleic acid molecules in cells using the lipid-containing particles provided herein, as well as cells and kits comprising the lipid-containing particles.
The embodiments disclosed herein utilized RNA targeting effectors to provide a robust CRISPR-based diagnostic with attomolar sensitivity. Embodiments disclosed herein can detect broth DNA and RNA with comparable levels of sensitivity and can differentiate targets from non-targets based on single base pair differences. Moreover, the embodiments disclosed herein can be prepared in freeze-dried format for convenient distribution and point-of-care (POC) applications. Such embodiments are useful in multiple scenarios in human health including, for example, viral detection, bacterial strain typing, sensitive genotyping, and detection of disease-associated cell free DNA.
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
C12P 19/34 - Polynucléotides, p. ex. acides nucléiques, oligoribonucléotides
C12Q 1/68 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismesCompositions à cet effetProcédés pour préparer ces compositions faisant intervenir des acides nucléiques
C12Q 1/6806 - Préparation d’acides nucléiques pour analyse, p. ex. pour test de réaction en chaîne par polymérase [PCR]
C12Q 1/6809 - Méthodes de détermination ou d’identification des acides nucléiques faisant intervenir la détection différentielle
C12Q 1/6811 - Méthodes de sélection pour la production ou l’élaboration d’oligonucléotides spécifiques cibles ou de molécules de liaison
C12Q 1/6816 - Tests d’hybridation caractérisés par les moyens de détection
C12Q 1/6876 - Produits d’acides nucléiques utilisés dans l’analyse d’acides nucléiques, p. ex. amorces ou sondes
G01N 33/00 - Recherche ou analyse des matériaux par des méthodes spécifiques non couvertes par les groupes
8.
THERAPEUTIC COMPOSITIONS FOR THE TREATMENT OF BACTERIAL VAGINOSIS AND METHODS OF USE THEREOF
Provided herein are compositions, systems, and methods for delivering cargo to a target cell. The compositions, systems, and methods comprise one or more polynucleotides encoding one or more LTR retroelement polypeptides for forming a delivery vesicle and one or more capture moieties for packaging a cargo within the delivery vesicle. The one or more LTR retroelement polypeptides for forming a delivery vesicle may comprise two or more of an LTR retroelement gag protein, a retroelement envelope protein, an LTR retroelement reverse transcriptase, or a combination thereof. The LTR retroelement polypeptide alone, the LTR retroelement envelope protein alone, or both the LTR retroelement-derived polypeptide and LTR retroelement envelope protein may be endogenous.
A61K 48/00 - Préparations médicinales contenant du matériel génétique qui est introduit dans des cellules du corps vivant pour traiter des maladies génétiquesThérapie génique
C07K 14/005 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant de virus
C07K 14/47 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'animauxPeptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'humains provenant de vertébrés provenant de mammifères
C07K 14/705 - RécepteursAntigènes de surface cellulaireDéterminants de surface cellulaire
C07K 16/18 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains
C07K 14/47 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'animauxPeptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'humains provenant de vertébrés provenant de mammifères
G01N 33/577 - Tests immunologiquesTests faisant intervenir la formation de liaisons biospécifiquesMatériaux à cet effet faisant intervenir des anticorps monoclonaux
A61P 29/00 - Agents analgésiques, antipyrétiques ou anti-inflammatoires non centraux, p. ex. agents antirhumatismauxMédicaments anti-inflammatoires non stéroïdiens [AINS]
11.
OPTICAL GENETIC SCREENS OF INTRACELLULAR AND INTERCELLULAR TRANSCRIPTIONAL CIRCUITS WITH PERTURB-FISH
The subject matter disclosed herein is generally directed to methods for highly multiplexed spatially resolved optical perturbation screening and kits thereof. The methods use sequence specific perturbations that can be amplified in situ and optically decoded. The perturbations can be paired with optically decoded gene expression data.
This invention is related to molecules and methods of use of said molecules or compounds comprising said molecules. A molecule may be a pomalidomide or a thalidomide analogue. A method of inducing degradation of a target protein comprising one or more zinc finger polypeptides in a cell may comprise exposing a cell transfected with the target protein with a molecule as described herein, a pharmaceutically acceptable salt thereof, or any combination thereof. A method of inducing degradation of a target protein comprising one or more FK506 binding protein (FKBP) domains or degradation of a target amine in a cell may comprise exposing a cell transfected with the target protein or comprising the target amine with a composition comprising a molecule as described herein, a pharmaceutically acceptable salt thereof, or any combination of compositions comprising molecules as described herein and pharmaceutically acceptable salts thereof. A method may improve on-target effects and reduce off-target effects.
C07D 401/14 - Composés hétérocycliques contenant plusieurs hétérocycles comportant des atomes d'azote comme uniques hétéro-atomes du cycle, au moins un cycle étant un cycle à six chaînons avec un unique atome d'azote contenant au moins trois hétérocycles
A61K 31/454 - Pipéridines non condensées, p. ex. pipérocaïne contenant d'autres systèmes hétérocycliques contenant un cycle à cinq chaînons avec l'azote comme hétéro-atome du cycle, p. ex. pimozide, dompéridone
A61K 31/4545 - Pipéridines non condensées, p. ex. pipérocaïne contenant d'autres systèmes hétérocycliques contenant un cycle à six chaînons avec l'azote comme hétéro-atome du cycle, p. ex. pipampérone, anabasine
A61K 31/496 - Pipérazines non condensées contenant d'autres hétérocycles, p. ex. rifampine, thiothixène ou sparfloxacine
A61K 31/497 - Pyrazines non condensées contenant d'autres hétérocycles
A61K 31/517 - PyrimidinesPyrimidines hydrogénées, p. ex. triméthoprime condensées en ortho ou en péri avec des systèmes carbocycliques, p. ex. quinazoline, périmidine
A61K 31/5377 - 1,4-Oxazines, p. ex. morpholine non condensées et contenant d'autres hétérocycles, p. ex. timolol
A61K 47/55 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament l’ingrédient non actif étant un agent de modification l’agent de modification étant un composé organique l’agent de modification étant aussi un agent pharmacologiquement ou thérapeutiquement actif, c.-à-d. le conjugué entier étant un co-médicament, p. ex. un dimère, un oligomère ou un polymère de composés pharmacologiquement ou thérapeutiquement actifs
C07D 401/04 - Composés hétérocycliques contenant plusieurs hétérocycles comportant des atomes d'azote comme uniques hétéro-atomes du cycle, au moins un cycle étant un cycle à six chaînons avec un unique atome d'azote contenant deux hétérocycles liés par une liaison directe de chaînon cyclique à chaînon cyclique
Disclosed herein are capped RNA transcripts comprising one or more modified nucleotides at position +3 or higher with reference to a 5' terminus of the RNA molecule, and methods of making the same. Also provided are compositions comprising one or more of the capped RNA transcripts provided herein, and methods of using said compositions for therapeutic applications.
14.
SELF-ASSEMBLING VIRUS-LIKE PARTICLES FOR DELIVERY OF PRIME EDITORS AND METHODS OF MAKING AND USING SAME
The present disclosure provides virus-like particles (VLPs) for delivering prime editors, and systems comprising such prime editor (PE) VLPs. The present disclosure also provides polynucleotides encoding the PE-VLPs described herein, which may be useful for producing said PE-VLPs. Also provided herein are methods for editing the genome of a target cell by introducing the presently described PE-VLPs into the target cell. The present disclosure also provides fusion proteins that make up a component of the PE-VLPs described herein, as well as polynucleotides, vectors, cells, and kits.
A61K 48/00 - Préparations médicinales contenant du matériel génétique qui est introduit dans des cellules du corps vivant pour traiter des maladies génétiquesThérapie génique
C12N 7/00 - Virus, p. ex. bactériophagesCompositions les contenantLeur préparation ou purification
C12N 9/12 - Transférases (2.) transférant des groupes contenant du phosphore, p. ex. kinases (2.7)
Nucleic acid molecules, compositions, recombinant AAV (rAAV) particles, kits, and methods are described herein for delivering a base editor (or “nucleobase editor”) to cells, e.g., via AAV vectors. In particular, the disclosure provides compositions, methods, and uses for delivery of adenine base editors and cytosine base editors in a single AAV vector (or genome). Further described herein are improved AAV vectors containing size-minimized regulatory components that enable, e.g., the packaging of base editors. Provided herein are methods and compositions for delivering base editor proteins to a cell or tissue in a single recombinant AAV (rAAV) vector. Contemplated herein are improved methods and compositions for delivering these base editors in vivo, in a single rAAV particle. Further provided herein are base editors and compositions and cells comprising these base editors.
A61K 48/00 - Préparations médicinales contenant du matériel génétique qui est introduit dans des cellules du corps vivant pour traiter des maladies génétiquesThérapie génique
C12N 9/80 - Hydrolases (3.) agissant sur les liaisons carbone-azote autres que les liaisons peptidiques (3.5) agissant sur les liaisons amides des amides aliphatiques
C12N 15/11 - Fragments d'ADN ou d'ARNLeurs formes modifiées
Described herein are engineered paraneoplastic Ma protein (PNMA) capable of forming a capsid. In some embodiments, the engineered PNMA proteins comprise one or more modifications that enhance binding or loading of a cargo into the capsid, one or more modifications that modify cell-specificity of the capsid, one or more modifications that enhance intracellular delivery of the capsid, or a combination thereof. Also described herein are delivery systems comprising capsids comprising an engineered PNMA protein and a cargo.
A61K 48/00 - Préparations médicinales contenant du matériel génétique qui est introduit dans des cellules du corps vivant pour traiter des maladies génétiquesThérapie génique
C12N 7/00 - Virus, p. ex. bactériophagesCompositions les contenantLeur préparation ou purification
Engineered capsid scaffolds comprising one or more modified capsid proteins are described exhibiting properties of improved thermostability while producing at similar levels to the naturally occurring capsid serotype. Embodiments include use and delivery of the engineered capsid scaffolds to allow for increased tolerance for manipulation and mutagenesis.
Some aspects of this disclosure provide strategies, systems, reagents, methods, and kits that are useful for the targeted editing of nucleic acids, including editing a single site within the genome of a cell or subject, e.g., within the human genome. The disclosure provides fusion proteins of nucleic acid programmable DNA binding proteins (napDNAbp), e.g., Cas9 or variants thereof, and nucleic acid editing proteins such as cytidine deaminase domains (e.g., novel cytidine deaminases generated by ancestral sequence reconstruction), and adenosine deaminases that deaminate adenine in DNA. Aspects of the disclosure relate to fusion proteins (e.g., base editors) that have improved expression and/or localize efficiently to the nucleus. In some embodiments, base editors are codon optimized for expression in mammalian cells. In some embodiments, base editors include multiple nuclear localization sequences (e.g., bipartite NLSs), e.g., at least two NLSs. In some embodiments, methods for targeted nucleic acid editing are provided.
C07K 14/47 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'animauxPeptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'humains provenant de vertébrés provenant de mammifères
This disclosure is directed to a targeted delivery vehicle that can deliver a cargo to a cell of interest. The targeted delivery vehicle has a fusogen and a targeting domain which are embedded in a lipid bilayer membrane that forms a vesicle, and a cargo within the vesicle. The disclosure is also directed to methods for targeted delivery of cargo using the targeted delivery vehicle described herein.
A61K 48/00 - Préparations médicinales contenant du matériel génétique qui est introduit dans des cellules du corps vivant pour traiter des maladies génétiquesThérapie génique
C07K 14/005 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant de virus
A61K 48/00 - Préparations médicinales contenant du matériel génétique qui est introduit dans des cellules du corps vivant pour traiter des maladies génétiquesThérapie génique
C07K 14/005 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant de virus
The present disclosure relates generally to the field of delivery systems using contractile injection systems (CIS). Specifically disclosed are engineered extracellular CISs (eCISs) that can deliver non-natural protein payloads to non-natural target cells such as human cells. In addition, methods of using the engineered eCISs are also disclosed.
Described herein are targeting moieties that can be capable of specifically targeting muscle cells and can include an n-mer motif. In some embodiments, the n-mer motif contains an RGD motif. Also described herein are vector systems, particles, polypeptides that can encode and/or contain one or more targeting moieties. Also described herein are methods of delivering a cargo to a cell, such as a muscle cell, using one or more of the targeting moieties described herein.
A61K 31/7088 - Composés ayant au moins trois nucléosides ou nucléotides
A61K 47/64 - Conjugués médicament-peptide, médicament-protéine ou médicament-acide polyaminé, c.-à-d. l’agent de modification étant un peptide, une protéine ou un acide polyaminé lié par covalence ou complexé à un agent thérapeutiquement actif
A61K 48/00 - Préparations médicinales contenant du matériel génétique qui est introduit dans des cellules du corps vivant pour traiter des maladies génétiquesThérapie génique
C07K 7/06 - Peptides linéaires ne contenant que des liaisons peptidiques normales ayant de 5 à 11 amino-acides
C07K 14/005 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant de virus
C07K 14/47 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'animauxPeptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'humains provenant de vertébrés provenant de mammifères
Disclosed herein are methods and systems utilizing CRISPR effector systems for assays and diagnostics. Embodiments herein provide tile probes in systems and methods for detection of multiple targets across a given genome or group of genomes, including in circulating nucleic acid samples.
C12Q 1/689 - Produits d’acides nucléiques utilisés dans l’analyse d’acides nucléiques, p. ex. amorces ou sondes pour la détection ou l’identification d’organismes pour les bactéries
C12Q 1/6818 - Tests d’hybridation caractérisés par les moyens de détection impliquant l’interaction de plusieurs marqueurs, p. ex. transfert d’énergie de résonance
Mammals rely on adaptive immunity to protect against infections and tumors, with the thymus playing a crucial role by producing T cells that target infected or cancerous cells. The thymus, however, undergoes functional decline with age, significantly impairing the immune system in the elderly. To investigate reversing this decline, compositions and methods for activation and differentiation of T cell progenitors in extrathymic tissues are disclosed that stimulate production of differentiated T cells. For example, LNP-mediated delivery of mRNAs encoding DLL-1, IL-7, and FLT3L to the liver is shown to create a temporary site for T cell maturation that enhances T cell-mediated immunity in aged mice without causing autoimmunity. This approach facilitates ectopic T cell development from hematopoietic precursors and activates dendritic cells, providing evidence that engineering adaptive immunity in vivo can effectively mitigate immune aging.
A61K 48/00 - Préparations médicinales contenant du matériel génétique qui est introduit dans des cellules du corps vivant pour traiter des maladies génétiquesThérapie génique
Described herein are muscle-specific targeting moieties and compositions including the muscle specific targeting motifs. Also described herein are uses of the muscle-specific targeting motifs and compositions including the muscle specific targeting moieties. In some embodiments, the muscle-specific targeting moieties and compositions including the muscle specific targeting moieties can be used to direct delivery of a cargo to a muscle cell.
A61K 48/00 - Préparations médicinales contenant du matériel génétique qui est introduit dans des cellules du corps vivant pour traiter des maladies génétiquesThérapie génique
A61P 21/00 - Médicaments pour le traitement des troubles du système musculaire ou neuromusculaire
26.
COMPOSITIONS AND METHODS FOR EFFICIENT IN VIVO DELIVERY
Disclosed herein are compositions, methods, kits, and systems relating to efficient delivery of cargos (e.g., therapeutic cargos) into cells, for instance, for in vivo delivery. The present disclosure provides lipid-containing particles (e.g., virus-like particles) for delivering therapeutic cargos. The present disclosure also provides polynucleotides encoding the lipid-containing particles provided herein, which may be useful for producing said lipid-containing particles. Also provided are methods for editing nucleic acid molecules in cells using the lipid-containing particles provided herein, as well as cells and kits comprising the lipid-containing particles.
Engineered or non-naturally occurring systems and compositions comprising novel Type V Cas polypeptides and orthologs thereof are disclosed herein. Also provided are methods of use for the novel Type V Cas polypeptide systems and compositions for reprogrammable targeting of nucleic acid and polynucleotide components.
The present disclosure relates to methods aimed towards non-invasive targeted genomic and epigenomic sequencing of spatially-defined cellular or subcellular region. More particularly, the present disclosure relates to methods of using photoselection to achieve non-invasive targeted genomic and epigenomic sequencing of spatially-defined cellular or subcellular regions, via the use of light-activated probes.
Provided are isolated enhancer element sequences that regulate and restrict expression of a transgene, such as a therapeutic gene, to certain neuronal cell types and/or populations in the brain and CNS. Therapeutic virus vectors containing the cloned enhancer element sequences, particularly, recombinant adeno-associated virus (rAAV) vectors, and a transgene are described. The rAAV vectors, compositions and methods are useful for treating subjects afflicted with neuropsychiatric and neuropathological diseases, disorders and conditions and symptoms thereof. The vectors can be used to restore normal cellular function, e.g., by restoring expression of certain genes to the appropriate interneuron or neuron target cell populations, to address the root cause of the disease, e.g., by restoring the excitation-inhibition balance in the neuronal cell or cell population.
A61K 48/00 - Préparations médicinales contenant du matériel génétique qui est introduit dans des cellules du corps vivant pour traiter des maladies génétiquesThérapie génique
The present disclosure relates to systems and methods for detecting circulating tumor DNA (ctDNA) and minimal residual disease in a patient sample..Aspects of the present disclosure relate to use of a classification module to assess whether a patient sample comprises ctDNA and minimal residual disease based, in part, on patient-specific inputs. The present disclosure is also related, at least in part, to a determination of whether a patient has cancer based on an output of the classification module.
The present disclosure provides Cas9 variants, and base editors comprising these variants, that recognize non-canonical protospacer adjacent motifs (PAMs) and have less restrictive PAM requirements for editing. The present disclosure provides Cas9 protein variants comprising one or more amino acid substitutions relative to wild-type Nme2Cas9. Fusion proteins comprising the Cas protein variants described herein are also provided by the present disclosure. Further provided herein are methods for editing a target nucleic acid using the Cas variants and fusion proteins provided herein. The present disclosure also provides guide RNAs, complexes, polynucleotides, cells, kits, and pharmaceutical compositions. Further described herein are phage-assisted continuous evolution (PACE) systems, vectors, methods, and devices.
The present invention provides methods, primers, and modified substrates that allow for the physical pairing of nucleic acid molecules together from a single source.
The present invention discloses high-throughput methods for the creation of antibodies or antigen-binding fragments that can bind to single or multiple targets. Also disclosed are methods for using one or more antibodies or antigen-binding fragments to detect cognate binding partners in various types of samples.
G01N 33/68 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique faisant intervenir des protéines, peptides ou amino-acides
36.
COMPOSITIONS AND METHODS FOR END TO END CAPTURE OF MESSENGER RNAS
Methods and compositions for a single- or multi-pot protocol for the efficient end to end capture of RNAs (inclusive of their poly-A tail or their 3′ end) is described. Capture oligonucleotides containing a 3′ non-extendable end and a selectively cleavable base upstream of an oligo-dT or oligo-dN and a 5′ sequence containing unique molecular identifiers, and 2) a deoxyuracil glycosylase that acts only on a deoxyuracil present in a DNA: DNA duplex or DNA/RNA heteroduplex are used. A dual template switching mechanism may be used.
The specification provides programmable base editors that are capable of introducing a nucleotide change and/or which could alter or modify the nucleotide sequence at a target site in mitochondrial DNA (mtDNA) with high specificity and efficiency. Moreover, the disclosure provides fusion proteins and compositions comprising a programmable DNA binding protein (e.g., a mitoTALE, a mitoZFP, or a CRISPR/Casp) and double-stranded DNA deaminase that is capable of being delivered to the mitochondria and carrying out precise installation of nucleotide changes in the mtDNA. The fusion proteins and compositions are not limited for use with mtDNA, but also may be used for base editing of any double-stranded target DNA.
Technion Research & Development Foundation Limited (Israël)
Inventeur(s)
Priebe, Gregory P.
Kishony, Roy
Chung, Hattie
Schaefers, Matthew M.
Abrégé
This disclosure relates to methods and compositions useful for detecting and monitoring low-frequency mutations. Methods and compositions described herein can be used to guide clinical decisions, for example, by informing on which antibiotics should be avoided, or conversely, which antibiotics should be actively used in the case of compounds that select against a specific type of resistance.
C12Q 1/689 - Produits d’acides nucléiques utilisés dans l’analyse d’acides nucléiques, p. ex. amorces ou sondes pour la détection ou l’identification d’organismes pour les bactéries
C12Q 1/6806 - Préparation d’acides nucléiques pour analyse, p. ex. pour test de réaction en chaîne par polymérase [PCR]
Described in several exemplary embodiments are compositions including a targeting moiety effective to target a central nervous system cell and formulations thereof. In certain embodiments, the targeting moiety is composed of one or more n-mer inserts, that can include one or more RGD motifs, and/or one or more P-motifs. Also described in certain example embodiments are vector systems configured to generate polypeptides containing the one or more targeting moieties. Also described herein are methods of generating a targeting moiety effective to target a central nervous system cell and using the compositions containing the targeting moieties described herein, such as to deliver a cargo to a subject and/or treat a central nervous system disease, disorder, or system thereof.
A61K 48/00 - Préparations médicinales contenant du matériel génétique qui est introduit dans des cellules du corps vivant pour traiter des maladies génétiquesThérapie génique
The disclosure provides agents that sensitize neoplastic cells through glycosylation by a glycosyltransferase. In the mechanism of cytotoxicity discussed herein, compounds become glycosylated resulting in comitant cytotoxicity. Exemplary compounds include: Compound 1 (BRD9645), Compound 2 ((R112), Compound 3 (Tioxolone), Compound 4 (Baf A1).
A61K 31/343 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine ayant des cycles à cinq chaînons avec un oxygène comme seul hétéro-atome d'un cycle, p. ex. isosorbide condensés avec un carbocycle, p. ex. coumarane, bufaralol, béfunolol, clobenfurol, amiodarone
C12Q 1/48 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismesCompositions à cet effetProcédés pour préparer ces compositions faisant intervenir une transférase
G01N 33/68 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique faisant intervenir des protéines, peptides ou amino-acides
G01N 33/574 - Tests immunologiquesTests faisant intervenir la formation de liaisons biospécifiquesMatériaux à cet effet pour le cancer
41.
REPROGRAMMABLE FANZOR POLYNUCLEOTIDES AND USES THEREOF
Systems, methods and composition for targeting polynucleotides are detailed herein. In particular, engineered DNA-targeting systems comprising novel Fanzor polypeptides and a reprogrammable targeting nucleic acid component and methods and application of use are described.
42.
METHODS AND COMPOSITIONS FOR EDITING A GENOME WITH PRIME EDITING AND A RECOMBINASE
Disclosed are constructs, systems, and methodologies using prime editing (PE), twin prime editing (twinPE), or multi-flap prime editing to carry out site-specific and large-scale genetic modification, such as, but not limited to, insertions, deletions, inversions, replacements, and chromosomal translocations of whole or partial genes (e.g., whole gene, gene exons and/or introns, and gene regulatory regions). In certain embodiments, the disclosure provides constructs, systems, and methods using prime editing (PE), e.g., single flap or “classical” PE or twinPE or multi-flap PE, to install one or more target sites for site specific recombination in a target genomic locus (e.g., a specific gene, exon, intron, or regulatory sequence), which may then be acted on by one or more site-specific recombinases to effectuate a large-scale genetic modification, such as an insertions, deletions, inversions, replacements, and chromosomal translocations.
The present disclosure provides compositions and methods for the targeted modification of RNA molecules by RNA prime editing. The compositions and methods may be conducted invitro or in vivo within cells (e.g., human cells) for the therapeutic correction of disease-causing mutations and/or installation of motifs or mutations in RNA molecules of interest as a tool for scientific research. The disclosure provides compositions and methods for conducting RNA prime editing of a target RNA molecule (e.g., an RNA transcript) that enables the incorporation of one or more nucleotide changes and/or targeted mutagenesis of a target RNA molecule. The nucleotide change can include a single-nucleotide change, an insertion of one or more nucleotides, or a deletion of one or more nucleotides. More in particular, the disclosure provides a variety of configurations of the RNA prime editors each comprising a nucleic acid programmable RNA binding proteins (napRNAbp), such as Cas13, and an RNA-dependent RNA polymerase (RDRP), which are provided as fusion proteins or which can be separately provided in trans. The RNA prime editors are guided to a target RNA site by a guide RNA, which can be a rpegRNA that includes a template region for the synthesis of an RNA sequence to be installed on the RNA molecule attached to an available 3′ terminus. In others embodiments, the RNA template can be provided in trans.
C07K 16/30 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire provenant de cellules de tumeurs
C12N 15/10 - Procédés pour l'isolement, la préparation ou la purification d'ADN ou d'ARN
C40B 30/04 - Procédés de criblage des bibliothèques en mesurant l'aptitude spécifique à se lier à une molécule cible, p. ex. liaison anticorps-antigène, liaison récepteur-ligand
C40B 30/06 - Procédés de criblage des bibliothèques en mesurant les effets sur des cellules, des tissus ou des organismes vivants
C40B 40/02 - Bibliothèques contenues ou présentées dans des micro-organismes, p. ex. des bactéries ou des cellules animalesBibliothèques contenues ou présentées dans des vecteurs, p. ex. des plasmidesBibliothèques contenant uniquement des micro-organismes ou des vecteurs
C40B 40/06 - Bibliothèques comprenant des nucléotides ou des polynucléotides ou leurs dérivés
45.
VHH POLYPEPTIDES THAT BIND TO MESOTHELIN, COMPOSITIONS AND METHODS OF USE THEREOF
Single domain VHH polypeptides (antibodies) that bind mesothelin, VHH polypeptide products, methods, cells, pharmaceutical compositions, and kits. The VHH polypeptides may be recombinantly produced and expressed. Provided are also chimeric antigen receptor (CAR) polypeptides comprising the VHH polypeptides and CAR immune effector cells comprising the expressing the same.
C07K 16/30 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire provenant de cellules de tumeurs
The present disclosure provides compounds of Formula I, and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled compounds, and prodrugs thereof. The provided compounds may be glycogen synthase kinase 3 (GSK3) inhibitors. The present disclosure also provides pharmaceutical compositions, combination therapies, and kits comprising the compounds, and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled compounds, or prodrugs thereof, and methods of treating or preventing diseases and disorders associated with GSK3.
A61P 25/18 - Antipsychotiques, c.-à-d. neuroleptiquesMédicaments pour le traitement de la manie ou de la schizophrénie
A61P 25/28 - Médicaments pour le traitement des troubles du système nerveux des troubles dégénératifs du système nerveux central, p. ex. agents nootropes, activateurs de la cognition, médicaments pour traiter la maladie d'Alzheimer ou d'autres formes de démence
A61K 31/4375 - Composés hétérocycliques ayant l'azote comme hétéro-atome d'un cycle, p. ex. guanéthidine ou rifamycines ayant des cycles à six chaînons avec un azote comme seul hétéro-atome d'un cycle condensés en ortho ou en péri avec des systèmes hétérocycliques le système hétérocyclique contenant un cycle à six chaînons ayant l'azote comme hétéro-atome du cycle, p. ex. quinolizines, naphtyridines, berbérine, vincamine
A61K 31/438 - Composés hétérocycliques ayant l'azote comme hétéro-atome d'un cycle, p. ex. guanéthidine ou rifamycines ayant des cycles à six chaînons avec un azote comme seul hétéro-atome d'un cycle le cycle étant condensé en spiro avec des systèmes carbocycliques ou hétérocycliques
Described in several exemplary embodiments are compositions including a targeting moiety effective to target a central nervous system cell and formulations thereof. In certain embodiments, the targeting moiety is composed of one or more n-mer inserts, that can include one or more RGD motifs, and/or one or more P-motifs. Also described in certain example embodiments are vector systems configured to generate polypeptides containing the one or more targeting moieties. Also described herein are methods of generating a targeting moiety effective to target a central nervous system cell and using the compositions containing the targeting moieties described herein, such as to deliver a cargo to a subject and/or treat a central nervous system disease, disorder, or system thereof.
A61K 48/00 - Préparations médicinales contenant du matériel génétique qui est introduit dans des cellules du corps vivant pour traiter des maladies génétiquesThérapie génique
C07K 14/005 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant de virus
Recent advances in the understanding of two CRISPR-Cas systems, namely, Type VI (Cas13a-d) and Type III (Type III-A-B), have shown both of them to have the ability to efficiently target RNA. Provided herein are compositions and methods for trans-splicing precursor mRNA using a catalytically-inactive Cas protein (dCas) and a trans-splicing construct comprising a guide RNA, an intron, a splice acceptor, donor RNA, and a poly A tail. The dCas is capable of forming a complex with the guide RNA and directing sequence-specific binding of the complex to a target precursor mRNA for genetic modification and any polypeptides derived thereof. The technology has important potential therapeutic applications such as correcting genetic mutations through exon replacement, insertion of transgenes, and increasing gene expression, and in non-therapeutic applications such as cell- and tissue-specific diagnostics.
The present disclosure provides compositions and methods for the selective transduction and genome editing of human cells (e.g., hematopoietic stem and progenitors cells, HSPCs) using engineered viral like particles (eVLPs). Aspects of the disclosure provide eVLP compositions comprising fusion proteins comprising a targeting moiety. In some embodiments, the fusion proteins comprise a cytokine conjugated to a transmembrane protein and/or an envelope glycoprotein. In other embodiments, the fusion proteins comprise a targeting moiety domain, a stalk protein domain, a transmembrane and/or envelope glycoprotein domain. Targeted-eVLP architectures comprising various targeting domains, stalk domains, transmembrane domains, and envelope glycoproteins are also provided herein. Other aspects of the disclosure provide eVLP compositions comprising envelope glycoproteins comprising non-natural sugars and methods of conjugating said eVLPs to various targeting moieties using bio-orthogonal click chemistry. Polynucleotides, vectors, cells, and kits useful for producing the articles, and performing the methods, described herein are also provided.
The disclosure features compositions and methods that are useful for determining the fraction of tumor-derived DNA (tumor fraction; TF) in cell free DNA (cfDNA). The methods involve calculating the fraction of tumor-derived DNA in the cfDNA using a combination of copy number alteration data and fragment length distribution data.
The present invention provides compounds for the treatment of a bacterial infection. Additionally, the present invention provides compositions and methods for using these compounds and compositions in the treatment of a bacterial infection in a subject.
C07D 205/04 - Composés hétérocycliques comportant des cycles à quatre chaînons ne contenant qu'un atome d'azote comme unique hétéro-atome du cycle non condensés avec d'autres cycles ne comportant pas de liaison double entre chaînons cycliques ou entre chaînons cycliques et chaînons non cycliques
A61K 31/397 - Composés hétérocycliques ayant l'azote comme hétéro-atome d'un cycle, p. ex. guanéthidine ou rifamycines ayant des cycles à quatre chaînons, p. ex. azétidine
A61P 31/06 - Agents antibactériens pour le traitement de la tuberculose
Immunogenic compositions comprising one or more peptides, wherein the one or more peptides: are capable of binding to Major Histocompatibility Complex (MHC) class II, and are derived from one or more translation products of SARS-CoV-2. Also provided include methods of treating and preventing diseases using the immunogenic compositions.
53.
EVOLVED DOUBLE-STRANDED DNA DEAMINASE BASE EDITORS AND METHODS OF USE
The specification provides programmable base editors that are capable of introducing a nucleotide change and/or which could alter or modify the nucleotide sequence at a target site in a double-stranded nucleotide sequence, such as, a chromosome, genome, or a mitochondrial DNA (mtDNA), with high specificity and efficiency. Moreover, the disclosure provides fusion proteins and compositions comprising a programmable DNA binding protein (e.g., a mitoTALE, a mitoZFP, or a CRISPR/Cas9) and evolved double-stranded DNA deaminase domains that is capable of being delivered to a cell nucleus and/or a mitochondria and carrying out precise installation of nucleotide changes in the target a double-stranded nucleotide sequence, such as, a chromosome, genome, or mtDNA. The fusion proteins and compositions are not limited for use with mtDNA, but may be used for base editing of any double-stranded target DNA.
Most disease-associated genetic loci map to more than one disease or trait, suggesting they act through multiple cell types and tissues giving rise to complex disease phenotypes. This pervasive pleiotropy of human diseases presents a tremendous burden on identifying mediating mechanisms and therapeutic targets. Multiple metabolic risk haplotypes are associated with risk for metabolic diseases. However, whether a haplotype actually causes a disease and the mechanisms that cause the disease are unknown. Integration of phenotypic and transcriptional profiling in primary human cells allows for functional characterization of disease-associated genetic variants. Applicants have analyzed multiple risk haplotypes and determined the function of risk haplotypes involved in causation of specific metabolic phenotypes, such as type 2 diabetes and lipodystrophy. Methods of treatments are disclosed herein.
A61K 48/00 - Préparations médicinales contenant du matériel génétique qui est introduit dans des cellules du corps vivant pour traiter des maladies génétiquesThérapie génique
A61K 38/17 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'animauxPeptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'humains
C12Q 1/6883 - Produits d’acides nucléiques utilisés dans l’analyse d’acides nucléiques, p. ex. amorces ou sondes pour les maladies provoquées par des altérations du matériel génétique
G01N 33/50 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique
55.
TUMOR AVATAR VACCINE COMPOSITIONS AND USES THEREOF
Disclosed herein are methods of eliciting an anti-cancer immune response by administering tumor-associated antigens, cells containing tumor-associated antigens, and/or nucleic acids encoding tumor-associated antigens. inducing immunogenic cell death in the cells expressing or containing the tumor-associated antigens. and optionally generating hyperactivated dendritic cells. Expression of tumor-associated antigens in a separate anatomical site generates a tumor avatar, which mimics the antigenic, but not immunosuppressive, environment of the tumor, with the generation of hyperactivated dendritic cells enhancing antigen presentation to elicit a robust anti-tumor T cell and antibody response. Also provided are compositions and kits containing nucleic acids and other components for use in the methods provided herein.
Described herein are pancreatic ductal adenocarcinoma (PDAC) signatures and methods of detecting the same in a sample from a subject. Also described herein, are methods of methods of diagnosing, prognosing, and/or treating PDAC in a subject that can include detecting one or more of the PDAC signatures.
C12Q 1/6886 - Produits d’acides nucléiques utilisés dans l’analyse d’acides nucléiques, p. ex. amorces ou sondes pour les maladies provoquées par des altérations du matériel génétique pour le cancer
G01N 33/50 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique
57.
SYSTEM, METHOD, AND PROGRAM PRODUCT FOR OUT OF DISTRIBUTION GENERALIZATION VIA INTERVENTIONAL STYLE TRANSFER
THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK (USA)
THE BROAD INSTITUTE, INC. (USA)
Inventeur(s)
Pernice, Wolfgang, M.
Hirano, Michio
Caicedo, Juan, C.
Abrégé
The present disclosure relates to a method for generating a training set based on a first set of images and a second set of images, each image having a respective observational environment and a respective feature set. The method includes (a) obtaining, by a generator module, the first set of images and the second set of images; (b) extracting, by the generator module, one or more feature sets from each image in the first set of images; (c) extracting, by the generator module, one or more respective observational environments from each image in the second set of images; (d) deriving, by an encoder module, one or more latent representations from the one or more feature sets extracted from one or more images in the first set of images; (e) deriving, by the encoder module, one or more style codes from the one or more respective observational environment extracted from one or more images in the second set of images; (f) generating, by the generator module, an interventional training distribution having samples including each respective one or more style codes and each one or more latent representations; and, (g) storing, by the generator module, the interventional training distribution training set.
Disclosed herein are modified mRNAs with poly(A) tails containing one or more additional poly-A tails or 5′ caps, which may be made by ligation of nucleic acids onto the 3′ terminal end or 5′ terminal end of an RNA, respectively. Also provided are compositions comprising one or more modified mRNAs provided herein, and methods of using said compositions for therapeutic or agricultural applications.
C12N 15/85 - Vecteurs ou systèmes d'expression spécialement adaptés aux hôtes eucaryotes pour cellules animales
C12N 15/88 - Introduction de matériel génétique étranger utilisant des procédés non prévus ailleurs, p. ex. co-transformation utilisant la micro-encapsulation, p. ex. utilisant des vésicules liposomiques
C12P 19/34 - Polynucléotides, p. ex. acides nucléiques, oligoribonucléotides
59.
METHODS OF PRODUCING LARGE-SCALE PLASMID LIBRARIES
C12N 15/70 - Vecteurs ou systèmes d'expression spécialement adaptés à E. coli
C40B 40/08 - Bibliothèques comprenant de l'ARN ou de l'ADN codant des protéines, p. ex. bibliothèques de gènes
C40B 40/02 - Bibliothèques contenues ou présentées dans des micro-organismes, p. ex. des bactéries ou des cellules animalesBibliothèques contenues ou présentées dans des vecteurs, p. ex. des plasmidesBibliothèques contenant uniquement des micro-organismes ou des vecteurs
C12N 15/65 - Introduction de matériel génétique étranger utilisant des vecteursVecteurs Utilisation d'hôtes pour ceux-ciRégulation de l'expression utilisant des marqueurs
e.ge.g., improved editing efficiency when used in the context of a prime editor). Fusion proteins, including for example prime editors, comprising the reverse transcriptase variants and Cas9 variants described herein are also provided by the present disclosure. The present disclosure also provides polynucleotides encoding the reverse transcriptase variants, Cas9 variants, and prime editors provided herein, as well as vectors comprising such polynucleotides. Pharmaceutical compositions and cells comprising the reverse transcriptase variants, Cas9 variants, and prime editors described herein are also provided by the present disclosure. The present disclosure also provides methods and uses involving the reverse transcriptase variants, Cas9 variants, and prime editors described herein.
The subject matter disclosed herein is generally directed to compositions and methods for multiplex decoding of quadruplet codons and methods for increasing the efficiency of quadruplet codon decoding using qtRNA evolution. Continuous evolution of qtRNAs is disclosed. Multiplex qtRNA constructs are disclosed.
An engineered AAV capsid is provided, in which at least one protein on the capsid is modified to include a n-mer motif, which promotes transduction of the capsid into the central nervous system (CNS). Further embodiments provide a vector system comprising one or more vectors encoding AAV capsids and a method of delivering cargo to the CNS. The method comprises administering, in vivo or in vitro, a AAV capsid according to embodiments described herein and the AVV capsid comprises one or more cargo molecules.
Described herein are engineered, non-naturally occurring systems and compositions comprising multimeric CRISPR-Cas complexes comprising a β-CASP polypeptide, a plurality of Cas polypeptides, and a guide molecule, packaging and delivery systems thereof, and methods of use thereof, for modifying target polynucleotides. In addition, described herein are engineered, non-naturally occurring systems and compositions comprising a class of small Cas proteins (Type II-B, II-C, and II-D Cas proteins) and methods of modifying target sequences using the Type II-B, II-C, II-D Cas proteins and systems thereof.
65.
Decoupled Encoder-Decoder Networks for Image Simulation and Modification
Decoupled encoder-decoder networks for image simulation and modification are described. An encoder network outputs feature representations of an input image of a biological sample, and a manipulation engine modifies the feature representations output by the encoder network by applying a variable associated with an experimental condition. A decoder network receives the modified feature representations from the manipulation engine and generates a simulated image by decoding the modified feature representations. The simulated image is a modified version of the input image that includes an estimated outcome of the experimental condition on the biological sample. The encoder network is trained separately from the decoder network, and the decoder network is adapted to the encoder network via at least one loss that is dependent on an output of the encoder network.
G06V 10/776 - ValidationÉvaluation des performances
G06V 10/772 - Détermination de motifs de référence représentatifs, p. ex. motifs de valeurs moyennes ou déformantsGénération de dictionnaires
G06V 10/774 - Génération d'ensembles de motifs de formationTraitement des caractéristiques d’images ou de vidéos dans les espaces de caractéristiquesDispositions pour la reconnaissance ou la compréhension d’images ou de vidéos utilisant la reconnaissance de formes ou l’apprentissage automatique utilisant l’intégration et la réduction de données, p. ex. analyse en composantes principales [PCA] ou analyse en composantes indépendantes [ ICA] ou cartes auto-organisatrices [SOM]Séparation aveugle de source méthodes de Bootstrap, p. ex. "bagging” ou “boosting”
G06V 10/778 - Apprentissage de profils actif, p. ex. apprentissage en ligne des caractéristiques d’images ou de vidéos
G06V 10/82 - Dispositions pour la reconnaissance ou la compréhension d’images ou de vidéos utilisant la reconnaissance de formes ou l’apprentissage automatique utilisant les réseaux neuronaux
G06V 20/69 - Objets microscopiques, p. ex. cellules biologiques ou pièces cellulaires
Aspects of the disclosure relate to non-naturally occurring polynucleotides encoding a Shank3 protein, AAV vectors comprising the polynucleotides, and gene therapy methods.
C07K 14/47 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'animauxPeptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'humains provenant de vertébrés provenant de mammifères
A61K 48/00 - Préparations médicinales contenant du matériel génétique qui est introduit dans des cellules du corps vivant pour traiter des maladies génétiquesThérapie génique
The present disclosure provides methods and systems for mapping gene and protein expression in a cell (i.e., mapping gene and protein expression within the same cell simultaneously). The present disclosure also provides methods for diagnosing a disease or disorder (e.g., a neurological disorder such as Alzheimer's disease) in a subject. Methods of screening for a candidate agent capable of modulating gene and/or protein expression are also provided by the present disclosure. The present disclosure also provides methods for treating a disease or disorder, such as Alzheimer's disease, in a subject in need thereof. A plurality of oligonucleotide probes, which may be useful for performing the methods described herein, are also described by the present disclosure, as well as kits comprising any of the oligonucleotide probes described herein. Additionally, the present disclosure provides methods, apparatuses, and non-transitory computer-readable storage media for identifying spatial variations of cell types in at least one image.
C12Q 1/6876 - Produits d’acides nucléiques utilisés dans l’analyse d’acides nucléiques, p. ex. amorces ou sondes
G01N 33/58 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique faisant intervenir des substances marquées
G01N 33/68 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique faisant intervenir des protéines, peptides ou amino-acides
68.
LIVE-CELL LABEL-FREE PREDICTION OF SINGLE-CELL OMICS PROFILES BY MICROSCOPY
Computer-implemented methods, computer program products, and systems determine an omics profiles of a cell using microscopy imaging data. In one aspect, a computer-implemented method determines an omics profiles of a cell using microscopy imaging data by a) receiving microscopy imaging data of a cell or a population of cells; b) determining a targeted expression profile of a set of target genes from the microscopy imaging data using a first machine learning model, the target genes identifying a cell type or cell state of interest; and c) determining a single-cell omics profile for the population of cells using a second machine learning algorithm model. The targeted expression profile and a reference single-cell RNA-seq data set are used as inputs for the second machine learning model. Computer-implemented methods, computer program products, and systems described herein also provide for determining single-cell omics profile from microscopy, such as Raman microscopy, or expression profiles, such as H&E stains.
G06V 20/69 - Objets microscopiques, p. ex. cellules biologiques ou pièces cellulaires
G06V 10/774 - Génération d'ensembles de motifs de formationTraitement des caractéristiques d’images ou de vidéos dans les espaces de caractéristiquesDispositions pour la reconnaissance ou la compréhension d’images ou de vidéos utilisant la reconnaissance de formes ou l’apprentissage automatique utilisant l’intégration et la réduction de données, p. ex. analyse en composantes principales [PCA] ou analyse en composantes indépendantes [ ICA] ou cartes auto-organisatrices [SOM]Séparation aveugle de source méthodes de Bootstrap, p. ex. "bagging” ou “boosting”
G06V 10/82 - Dispositions pour la reconnaissance ou la compréhension d’images ou de vidéos utilisant la reconnaissance de formes ou l’apprentissage automatique utilisant les réseaux neuronaux
G16B 25/10 - Profilage de l’expression de gènes ou de protéinesEstimation ou normalisation de ratio d’expression
Provided herein are methods and compositions related to the treatment or prevention of vascular disease and/or heart disease using biomarkers of ADAMTS7 activity and antagonists of ADAMTS7.
C12Q 1/37 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismesCompositions à cet effetProcédés pour préparer ces compositions faisant intervenir une hydrolase faisant intervenir une peptidase ou une protéinase
G01N 33/68 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique faisant intervenir des protéines, peptides ou amino-acides
70.
COMPOUNDS, COMPOSITIONS AND METHODS FOR CANCER PATIENT STRATIFICATION AND CANCER TREATMENT
The present invention features improved compounds, especially
The present invention features improved compounds, especially
The present invention features improved compounds, especially
methods of identifying patients having cancer using biomarkers (e.g., PDE3A, SLFN12 and/or CREB3L1) that correlate with drug sensitivity and consequently treating a stratified patient population with an agent of the invention (e.g., Compounds 1-6 disclosed herein).
C07D 413/10 - Composés hétérocycliques contenant plusieurs hétérocycles, au moins un cycle comportant des atomes d'azote et d'oxygène comme uniques hétéro-atomes du cycle contenant deux hétérocycles liés par une chaîne carbonée contenant des cycles aromatiques
42 - Services scientifiques, technologiques et industriels, recherche et conception
Produits et services
Scientific research; scientific laboratory services;
scientific laboratory services in the field of genomics;
research and development services in the field of genomics;
research and development services in the field of genomics,
namely, sequencing DNA and RNA; sample collection and
preparation for scientific research purposes.
THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK (USA)
THE BROAD INSTITUTE, INC. (USA)
PRESIDENT AND FELLOWS OF HARVARD COLLEGE (USA)
Inventeur(s)
Quinn, Peter M. J.
Lopes Da Costa, Bruna
Tsang, Stephen H.
Liu, David R.
Abrégé
The present disclosure provides systems, methods, and compositions for modifying the crumbs homologue-1 gene. Particularly the present disclosure provides systems, methods, and compositions for prime editing insertion or correction of mutations in the crumbs homologue-1 gene.
The present disclosure features methods for modifying fertility. In some embodiments, the disclosure provides contraceptive compositions and methods of using the same.
09 - Appareils et instruments scientifiques et électriques
42 - Services scientifiques, technologiques et industriels, recherche et conception
Produits et services
Downloadable genomic and non-genomic datasets for cancer
research. Providing on-line non-downloadable software for data
analysis, perturbational (drug, compound, genetic reagent,
biologic) screening results for scientific research
purposes, genomic and other omics results for scientific
research purposes, and genome-scale pooled genetic
perturbation (using RNAi, CRISPR or other genetic means)
screening results for scientific research purposes;
biomedical research services; biomedical research services
in connection with profiling for identifying genes and
biomarkers relevant for cancer.
The embodiments disclosed herein utilized RNA targeting effectors to provide a robust CRISPR-based diagnostic with attomolar sensitivity. Embodiments disclosed herein can detect both DNA and RNA with comparable levels of sensitivity and can differentiate targets from non-targets based on single base pair differences. Moreover, the embodiments disclosed herein can be prepared in freeze-dried format for convenient distribution and point-of-care (POC) applications. Such embodiments are useful in multiple scenarios in human health including, for example, viral detection, bacterial strain typing, sensitive genotyping, and detection of disease-associated cell free DNA.
42 - Services scientifiques, technologiques et industriels, recherche et conception
Produits et services
Scientific research; scientific laboratory services;
scientific laboratory services in the field of genomics;
research and development services in the field of genomics;
research and development services in the field of genomics,
namely, sequencing DNA and RNA; sample collection and
preparation for scientific research purposes.
78.
METHODS AND COMPOSITIONS FOR ANALYSIS AND TREATMENT OF REPEAT EXPANSION DISORDERS
Methods and compositions for analysis and treatment of repeat expansion disorders are described. Labeled amplicons of a variable repeat region of a gene may be generated, said generating using primers that introduce at least one molecular label to respective nucleic acid molecules of origin of a biological sample. The labeled amplicons may be sequenced to generate sequencing reads having the at least one molecular label incorporated. A sequence repeat length distribution of the variable repeat region in at least a portion of the biological sample may be generated based on the sequencing reads.
The Trustees of Columbia University in the City of New York (USA)
The Broad Institute, Inc. (USA)
Inventeur(s)
Quinn, Peter M.J.
Lopes Da Costa, Bruna
Tsang, Stephen H.
Liu, David R.
Abrégé
The present disclosure provides systems, methods, and compositions for modifying the crumbs homologue-1 gene. Particularly the present disclosure provides systems, methods, and compositions for prime editing insertion or correction of mutations in the crumbs homologue-1 gene.
09 - Appareils et instruments scientifiques et électriques
42 - Services scientifiques, technologiques et industriels, recherche et conception
Produits et services
Downloadable genomic and non-genomic datasets for cancer
research. Providing on-line non-downloadable software for data
analysis, perturbational (drug, compound, genetic reagent,
biologic) screening results for scientific research
purposes, genomic and other omics results for scientific
research purposes, and genome-scale pooled genetic
perturbation (using RNAi, CRISPR or other genetic means)
screening results for scientific research purposes;
biomedical research services; biomedical research services
in connection with profiling for identifying genes and
biomarkers relevant for cancer.
81.
RIBOSOMAL RNA (rRNA) VARIANTS POSSESSING ENHANCED PROTEIN PRODUCTION CAPABILITIES
The present disclosure relates to compositions, methods and kits for enhancing ribosomal activities in a host cell, especially improvement of the translation activity of heterologous ribosomes within a host cell. Specifically, the instant disclosure provides a number of evolved rRNA sequences, which were remarkably identified to possess enhanced translation activities, improved orthogonal-ribosome binding site (o-RBS) and orthogonal anti-ribosome binding site (o-antiRBS) sequences, host cells possessing deletion or disruption of ribosome hibernation promoting factor (HPF) that thereby exhibit enhanced propagation of selection phage constructs during (PACE), among other aspects. New transgenic organisms harboring heterologous ribosomes and operons are also provided.
The present disclosure provides methods, compositions, and systems for evolving virus-like particles (VLPs) having one or more desired properties such as increased production levels, increased cargo packaging efficiency, and/or increased transduction of particular target cell types of interest. The present disclosure also provides libraries for use in such methods, and methods for producing the libraries. Group specific antigen (gag) proteins comprising nucleocapsid protein variants evolved using the methods described herein are also provided herein. The present disclosure also provides VLPs comprising such gag proteins comprising nucleocapsid protein variants. Polynucleotides, vectors, cells, and kits useful for performing the methods described herein are also provided.
C40B 20/04 - Identification des éléments d'une bibliothèque au moyen d'une étiquette, d'un marqueur ou d'un autre identificateur lisible ou détectable, p. ex. procédés de décodage
C40B 40/02 - Bibliothèques contenues ou présentées dans des micro-organismes, p. ex. des bactéries ou des cellules animalesBibliothèques contenues ou présentées dans des vecteurs, p. ex. des plasmidesBibliothèques contenant uniquement des micro-organismes ou des vecteurs
C40B 40/06 - Bibliothèques comprenant des nucléotides ou des polynucléotides ou leurs dérivés
C40B 40/08 - Bibliothèques comprenant de l'ARN ou de l'ADN codant des protéines, p. ex. bibliothèques de gènes
83.
PANELS AND METHODS FOR DIAGNOSING AND TREATING LUNG CANCER
The disclosure provides molecular classifiers for use in the characterization and diagnosis of lung cancer and methods of selecting and treating subjects with appropriate personalized cancer treatments, including but not limited to CDK4/6 inhibitors, c-Met inhibitors, PD-1/PD-L1 inhibitors and combinations thereof.
C12Q 1/6886 - Produits d’acides nucléiques utilisés dans l’analyse d’acides nucléiques, p. ex. amorces ou sondes pour les maladies provoquées par des altérations du matériel génétique pour le cancer
Engineered Type V Cas polypeptides with reduced immunogenicity, CRISPR-Cas systems thereof, compositions thereof, delivery systems thereof, and methods of use thereof for modifying target polynucleotides, such as, for example, in cells.
A61K 48/00 - Préparations médicinales contenant du matériel génétique qui est introduit dans des cellules du corps vivant pour traiter des maladies génétiquesThérapie génique
C07K 14/195 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant de bactéries
C12N 15/52 - Gènes codant pour des enzymes ou des proenzymes
C12N 15/90 - Introduction stable d'ADN étranger dans le chromosome
Engineered Type II Cas polypeptides with reduced immunogenicity, CRISPR-Cas systems thereof, compositions thereof, delivery systems thereof, and methods of use thereof for modifying target polynucleotides, such as, for example, in cells.
Systems and methods for rapid diagnostics related to the use of combinations of CRISPR effector systems with optimized guide sequences, OSD probes, RNA probes and/or RNase H for detection of nucleic acid sequences, such as sequences from coronavirus, as well as multiplex lateral flow diagnostic devices and methods of use, are provided.
C12Q 1/70 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismesCompositions à cet effetProcédés pour préparer ces compositions faisant intervenir des virus ou des bactériophages
C12Q 1/6806 - Préparation d’acides nucléiques pour analyse, p. ex. pour test de réaction en chaîne par polymérase [PCR]
C12Q 1/6818 - Tests d’hybridation caractérisés par les moyens de détection impliquant l’interaction de plusieurs marqueurs, p. ex. transfert d’énergie de résonance
87.
METHODS AND COMPOSITIONS FOR PRIME EDITING NUCLEOTIDE SEQUENCES
Compositions and methods are provided herein for conducting prime editing of a target DNA molecule (e.g., a genome) that enables the incorporation of a nucleotide change and/or targeted mutagenesis. The compositions include fusion proteins comprising nucleic acid programmable DNA binding proteins (napDNAbp) and a polymerase (e.g., reverse transcriptase), which is guided to a specific DNA sequence by a modified guide RNA, named an PEgRNA. The PEgRNA has been altered (relative to a standard guide RNA) to comprise an extended portion that provides a DNA synthesis template sequence which encodes a single strand DNA flap which is synthesized by the polymerase of the fusion protein and which becomes incorporated into the target DNA molecule.
Highly selective targeting moieties and compositions comprising the targeting moieties are described herein to efficiently transduce endothelial cell of the central nervous system vasculature. Embodiments include use and delivery of the targeting moieties and compositions to selectively direct delivery of cargo.
A61K 48/00 - Préparations médicinales contenant du matériel génétique qui est introduit dans des cellules du corps vivant pour traiter des maladies génétiquesThérapie génique
A61K 31/7105 - Acides ribonucléiques naturels, c.-à-d. contenant uniquement des riboses liés à l'adénine, la guanine, la cytosine ou l'uracile et ayant des liaisons 3'-5' phosphodiester
A61K 47/64 - Conjugués médicament-peptide, médicament-protéine ou médicament-acide polyaminé, c.-à-d. l’agent de modification étant un peptide, une protéine ou un acide polyaminé lié par covalence ou complexé à un agent thérapeutiquement actif
The present disclosure provides methods for treating sickle cell disease using prime editing. The present disclosure also provides epegRNAs targeting the β-globin (HBB) gene, which may be useful for treating sickle cell disease. Also provided herein are prime editor complexes, polynucleotides, vectors, pharmaceutical compositions, kits, and cells useful for performing the methods described herein.
Systems and methods for targeted gene modification, targeted insertion, perturbation of gene transcripts, and nucleic acid editing. Novel nucleic acid targeting systems comprise components of CRISPR systems and transposable elements.
Systems and methods for targeted gene modification, targeted insertion, perturbation of gene transcripts, and nucleic acid editing. Novel nucleic acid targeting systems comprise components of CRISPR systems and non-LTR retrotransposon elements.
C12N 15/74 - Vecteurs ou systèmes d'expression spécialement adaptés aux hôtes procaryotes autres que E. coli, p. ex. Lactobacillus, Micromonospora
A61K 31/711 - Acides désoxyribonucléiques naturels, c.-à-d. contenant uniquement des 2'-désoxyriboses liés à l'adénine, la guanine, la cytosine ou la thymine et ayant des liaisons 3'-5' phosphodiester
92.
METHODS AND COMPOSITIONS FOR DISSECTING ORGANELLE PHYSIOLOGY
The subject matter disclosed herein is generally directed to methods for detailed organelle functional measurements in cell-based genetic screening assays. Specifically, disclosed herein are methods for combining detailed bioenergetics measurements with cell-based genetic-screening for mutant phenotypes.
C12Q 1/6806 - Préparation d’acides nucléiques pour analyse, p. ex. pour test de réaction en chaîne par polymérase [PCR]
C12Q 1/6897 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismesCompositions à cet effetProcédés pour préparer ces compositions faisant intervenir des acides nucléiques faisant intervenir des gènes rapporteurs liés de façon fonctionnelle à des promoteurs
The technology described herein provides tissue dissociation well plates, devices, systems, and kits to isolate single-cells or a single-nuclei using wells with roughened, angled bottom surfaces to receive pipette tips delivering tissue samples and isolation buffers. In certain examples, the bottom surfaces of the wells are roughened to aid in breaking down the tissue sample. In other examples, the tip of the pipette is roughened or serrated to aid in breaking down the tissue sample. The wells may be arrayed in a solid rigid upper surface. The pipette tips deliver isolation buffers and/or dissociation fluids to the wells and the tissue samples. The fluid delivery is provided by pumps via one or more perfusion manifolds. A pipette adaptor raises, lowers, and twists the pipette tips. The pipette tips deliver the dissociation fluid, withdraw the tissue samples with a suction force, and return the tissue samples to the well with an expelling force. The pipette tips may be twisted to provide an additional force to break down the tissue sample.
SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH (USA)
MEMORIAL HOSPITAL FOR THE TREATMENT OF CANCER AND ALLIED DISEASES (USA)
GENOME RESEARCH LIMITED (Royaume‑Uni)
Inventeur(s)
Petljak, Mia
Stratton, Michael R.
Maciejowski, John
Abrégé
The present disclosure provides methods for treating cancer in a subject (by inhibiting e.g., APOBEC3A, APOBEC3B, or REV1), and methods of diagnosing cancer in a subject. Methods of tracking mutagenesis induced by a gene of interest (e.g., APOBEC3A, APOBEC3B, or REV1) and methods of screening for inhibitors and synthetic lethalities are also described herein. Further provided by the present disclosure are cell lines and antibodies for use in the methods described herein.
C12Q 1/6886 - Produits d’acides nucléiques utilisés dans l’analyse d’acides nucléiques, p. ex. amorces ou sondes pour les maladies provoquées par des altérations du matériel génétique pour le cancer
C07K 16/40 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre des enzymes
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
G01N 33/50 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique
95.
METHODS FOR DIFFERENTIATING AND SCREENING STEM CELLS
The subject matter disclosed herein is generally directed to methods of differentiating pluripotent cells into target cell types and screening platforms for systematically identifying transcription factors (TFs) that drive differentiation of pluripotent cells into target cell types. Also disclosed is a high-throughput multiplex screening platform. Also disclosed are in vitro models for neural progenitor cells and cardiomyocytes.
A61K 35/30 - NerfsCerveauYeuxCellules cornéennesLiquide céphalorachidienCellules souches neuronalesCellules précurseurs neuronalesCellules glialesOligodendrocytesCellules de SchwannAstrogliesAstrocytesPlexus choroïdeTissu de moelle épinière
C12Q 1/6809 - Méthodes de détermination ou d’identification des acides nucléiques faisant intervenir la détection différentielle
C12Q 1/6881 - Produits d’acides nucléiques utilisés dans l’analyse d’acides nucléiques, p. ex. amorces ou sondes pour le typage de tissu ou de cellule, p. ex. sondes d’antigène leucocytaire humain [HLA]
42 - Services scientifiques, technologiques et industriels, recherche et conception
Produits et services
(1) Scientific research; scientific laboratory services; scientific laboratory services in the field of genomics; research and development services in the field of genomics; research and development services in the field of genomics, namely, sequencing DNA and RNA; sample collection and preparation for scientific research purposes.
42 - Services scientifiques, technologiques et industriels, recherche et conception
Produits et services
(1) Scientific research; scientific laboratory services; scientific laboratory services in the field of genomics; research and development services in the field of genomics; research and development services in the field of genomics, namely, sequencing DNA and RNA; sample collection and preparation for scientific research purposes.
98.
RETARGETED RETROVIRAL VECTORS RESISTANT TO VACCINE-INDUCED NEUTRALIZATION AND COMPOSITIONS OR METHODS OF USE THEREOF
The invention features pseudotyped viral particles (e.g., lentiviral or gammaretroviral particles) and compositions and methods of use thereof, where the viral particles comprise a VHH domain.
A61K 48/00 - Préparations médicinales contenant du matériel génétique qui est introduit dans des cellules du corps vivant pour traiter des maladies génétiquesThérapie génique
A61K 47/68 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament l’ingrédient non actif étant un agent de modification l’agent de modification étant un anticorps, une immunoglobuline ou son fragment, p. ex. un fragment Fc
A61K 47/69 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament le conjugué étant caractérisé par sa forme physique ou sa forme galénique, p. ex. émulsion, particule, complexe d’inclusion, stent ou kit
Compounds of formula (I), processes for their production and their use as pharmaceuticals are described herein.
Compounds of formula (I), processes for their production and their use as pharmaceuticals are described herein.
A61K 31/444 - Pyridines non condenséesLeurs dérivés hydrogénés contenant d'autres systèmes hétérocycliques contenant un cycle à six chaînons avec l'azote comme hétéro-atome du cycle, p. ex. amrinone
A61K 45/06 - Mélanges d'ingrédients actifs sans caractérisation chimique, p. ex. composés antiphlogistiques et pour le cœur
C12Q 1/6886 - Produits d’acides nucléiques utilisés dans l’analyse d’acides nucléiques, p. ex. amorces ou sondes pour les maladies provoquées par des altérations du matériel génétique pour le cancer
G01N 33/574 - Tests immunologiquesTests faisant intervenir la formation de liaisons biospécifiquesMatériaux à cet effet pour le cancer
100.
BIFIDOBACTERIUM LONGUM TRANSITIONAL MICROORGANISMS, COMPOSITIONS AND USES THEREOF
Described in several exemplary embodiments are Bifidobacterium longum subspecies, microorganisms and formulations thereof. Described in several exemplary embodiments are formulations, such as synthetic formulations, that contain one or more of the Bifidobacterium longum subspecies microorganisms. Described in several embodiments herein is use of the Bifidobacterium longum subspecies microorganisms and formulations thereof, such as in an infant and/or young child.
