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 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving transferase
C12N 9/00 - Enzymes, e.g. ligases (6.)ProenzymesCompositions thereofProcesses for preparing, activating, inhibiting, separating, or purifying 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 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for detection or identification of organisms for bacteria
C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
C12Q 1/6837 - Enzymatic or biochemical coupling of nucleic acids to a solid phase using probe arrays or probe chips
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 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for tissue or cell typing, e.g. human leukocyte antigen [HLA] probes
C07K 1/22 - Affinity chromatography or related techniques based upon selective absorption processes
C07K 14/195 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria
C07K 14/74 - Major histocompatibility complex [MHC]
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.
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 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
C07K 14/005 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from viruses
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
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 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
A61K 31/4545 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61K 47/55 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
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.
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.
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.
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 having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
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.
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 - Compounds having three or more nucleosides or nucleotides
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
C07K 7/06 - Linear peptides containing only normal peptide links having 5 to 11 amino acids
C07K 14/005 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from viruses
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
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 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for detection or identification of organisms for bacteria
C12Q 1/6818 - Hybridisation assays characterised by the detection means involving interaction of two or more labels, e.g. resonant energy transfer
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.
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.
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.
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 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.
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.
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.
Technion Research & Development Foundation Limited (Israel)
Inventor
Priebe, Gregory P.
Kishony, Roy
Chung, Hattie
Schaefers, Matthew M.
Abstract
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 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for detection or identification of organisms for bacteria
C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
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.
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 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
C12Q 1/48 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving transferase
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for 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.
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.
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.
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
C40B 30/04 - Methods of screening libraries by measuring the ability to specifically bind a target molecule, e.g. antibody-antigen binding, receptor-ligand binding
C40B 30/06 - Methods of screening libraries by measuring effects on living organisms, tissues or cells
C40B 40/02 - Libraries contained in or displayed by microorganisms, e.g. bacteria or animal cellsLibraries contained in or displayed by vectors, e.g. plasmidsLibraries containing only microorganisms or vectors
C40B 40/06 - Libraries containing nucleotides or polynucleotides, or derivatives thereof
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 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
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 - Antipsychotics, i.e. neurolepticsDrugs for mania or schizophrenia
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
A61K 31/4375 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring hetero atom, e.g. quinolizines, naphthyridines, berberine, vincamine
A61K 31/438 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring being spiro-condensed with carbocyclic or heterocyclic ring systems
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.
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 - Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
A61K 31/397 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having four-membered rings, e.g. azetidine
A61P 31/06 - Antibacterial agents for tuberculosis
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 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
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 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
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)
Inventor
Pernice, Wolfgang, M.
Hirano, Michio
Caicedo, Juan, C.
Abstract
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 - Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
C12N 15/88 - Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation using microencapsulation, e.g. using liposome vesicle
C12P 19/34 - Polynucleotides, e.g. nucleic acids, oligoribonucleotides
59.
METHODS OF PRODUCING LARGE-SCALE PLASMID LIBRARIES
C12N 15/70 - Vectors or expression systems specially adapted for E. coli
C40B 40/08 - Libraries containing RNA or DNA which encodes proteins, e.g. gene libraries
C40B 40/02 - Libraries contained in or displayed by microorganisms, e.g. bacteria or animal cellsLibraries contained in or displayed by vectors, e.g. plasmidsLibraries containing only microorganisms or vectors
C12N 15/65 - Introduction of foreign genetic material using vectorsVectorsUse of hosts thereforRegulation of expression using markers
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.
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 having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
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.
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.
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 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving hydrolase involving peptidase or proteinase
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
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 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
42 - Scientific, technological and industrial services, research and design
Goods & 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)
Inventor
Quinn, Peter M. J.
Lopes Da Costa, Bruna
Tsang, Stephen H.
Liu, David R.
Abstract
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 - Scientific and electric apparatus and instruments
42 - Scientific, technological and industrial services, research and design
Goods & 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 - Scientific, technological and industrial services, research and design
Goods & 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)
Inventor
Quinn, Peter M.J.
Lopes Da Costa, Bruna
Tsang, Stephen H.
Liu, David R.
Abstract
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 - Scientific and electric apparatus and instruments
42 - Scientific, technological and industrial services, research and design
Goods & 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 - Identifying library members by means of a tag, label, or other readable or detectable entity associated with the library members, e.g. decoding processes
C40B 40/02 - Libraries contained in or displayed by microorganisms, e.g. bacteria or animal cellsLibraries contained in or displayed by vectors, e.g. plasmidsLibraries containing only microorganisms or vectors
C40B 40/06 - Libraries containing nucleotides or polynucleotides, or derivatives thereof
C40B 40/08 - Libraries containing RNA or DNA which encodes proteins, e.g. gene libraries
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 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for 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.
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 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving virus or bacteriophage
C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
C12Q 1/6818 - Hybridisation assays characterised by the detection means involving interaction of two or more labels, e.g. resonant energy transfer
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 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
A61K 31/7105 - Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
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 - Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora
A61K 31/711 - Natural deoxyribonucleic acids, i.e. containing only 2'-deoxyriboses attached to adenine, guanine, cytosine or thymine and having 3'-5' phosphodiester links
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.
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 (United Kingdom)
Inventor
Petljak, Mia
Stratton, Michael R.
Maciejowski, John
Abstract
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 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
C07K 16/40 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against enzymes
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.
C12Q 1/6809 - Methods for determination or identification of nucleic acids involving differential detection
C12Q 1/6881 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for tissue or cell typing, e.g. human leukocyte antigen [HLA] probes
42 - Scientific, technological and industrial services, research and design
Goods & 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 - Scientific, technological and industrial services, research and design
Goods & 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 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
A61K 47/69 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or 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 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for 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.
