Abstract: Provides are modified immune cells including tumor infiltrating lymphocyte (TIL) or B cells, a compositions comprising the immune cells, and a method of treating neoplastic or cancer conditions comprising administering to a subject the immune cells.

Abstract: The present disclosure provides methods for genetically engineering T cells, such as CD4+ T cells, for use in cell therapy. In some aspects, the provided methods include one or more steps for incubating the cells under stimulating conditions, introducing a recombinant polypeptide to the cells through transduction or transfection, and cultivating the cells under conditions that promote proliferation and/or expansion. In some aspects, the incubation and/or the cultivation is performed in the presence of recombinant IL-2. In some aspects, the provided methods are an efficient, reliable means to produce genetically engineered T cells with a high degree of success.

Abstract: This invention relates to methods of expanding T regulatory cells through OX40L and Jagged-1 induced signaling. The methods can be used for treating autoimmune diseases.

Abstract: Compositions, methods and uses of genetically modified NK cells to treat a patient with a tumor are presented. The genetically modified NK cells express a protein complex having an a chain and a ? chain T cell receptor, at least a portion of which is specific to a patient- or tumor-specific neoepitope, or a tumor associated antigen, and at least a portion of CD3?, and at least a portion of CD3?. The genetically modified NK cells can be administered to a cancer patient to induce, maintain or augment a T cell immune response against the cancer or the tumor.

Abstract: The present invention chiefly aims to provide a process for directly inducing cardiomyocytes from somatic cells without performing artificial gene transfer, a cardiomyocyte obtained thereby, and a composition comprising a combination of chemical compounds capable of using for the said process. The present invention can include a process for producing a cardiomyocyte by inducing differentiation directly from a somatic cell, the process comprising a step of culturing the somatic cell in the presence of a MEK inhibitor and a cAMP inducer, and a cardiomyocyte obtained thereby, and then a composition for producing a cardiomyocyte by inducing differentiation directly from a somatic cell, the composition comprising a MEK inhibitor and a cAMP inducer. The cardiomyocytes obtained according to the present invention are useful in regenerative medicine and the like.

Abstract: Methods of using a small molecule MYH11 agonist to inhibit intimal hyperplasia and to maintain a contractile phenotype in vitro and in vivo are described. Also described herein are methods for generating human contractile smooth muscle cells from human pluripotent stem cells under defined conditions in the presence of the small molecule MYH11 agonist.

Abstract: The application discloses a method for obtaining MSC-derived cells with improved transplantation properties from MSC, the method comprising a cell size reduction step, wherein said cell size reduction step is characterized by contacting MSC or MSC-derived cells in vitro or ex vivo with heparin or a derivative or analogue thereof at a concentration of at least 0.01 IU/ml. The application further provides a method for obtaining mesenchymal stem cell-derived cells from mesenchymal stem cells (MSC) comprising contacting MSC in vitro or ex vivo with FGF-2, TGF? and at least 0.01 IU/ml heparin or a derivative or analogue thereof. The invention also provides the so-obtained cells and cell populations, as well as further products comprising such and uses thereof.

Abstract: This application describes liver stem cells (LSC), and differentiated hepatocytes, cholangiocytes, and 3D cellular structures derived therefrom. Methods for producing LSC and mature, differentiated hepatocytes and cholangiocytes in culture are provided. Also provided are cell culture systems and cell culture media for producing a homogenous population of liver stem cells that remain in an undifferentiated state over multiple passages in culture. The LSC and methods are useful for producing homogenous populations of hepatocytes and cholangiocytes for downstream applications. The LSC can be transplanted into subjects to treat liver diseases.

Abstract: The invention discloses for the first time pluripotent cells, including hypoimmune pluripotent ABO blood type O Rhesus Factor negative (HIPO?) cells, that evade rejection by the host allogeneic immune system and avoid blood antigen type rejection. The HIPO? cells comprise reduced HLA-I and HLA-II expression, increased CD47 expression, and a universal blood group O Rh?(“O?”) blood type. The universal blood type is achieved by eliminating ABO blood group A and B antigents as well as eliminating Rh factor expression, or by starting with an O? parent cell line. These new, novel HIPO? cells evade host immune rejection because they have an impaired antigen presentation capacity, protection from innate immune clearance, and lack blood group rejection. The cells of the invention also include O? pluripotent stem cells (iPSCO?) and O? embryonic stem cells (ESCO?).

Abstract: A method for vascular regeneration comprises delivering endothelial cells to a lung scaffold, delivering perivascular cells to the lung scaffold, and providing a multiphase culture program to the scaffold. The multiphase culture program comprises a first phase including delivering an angiogenic medium, e.g., having 40-100 ng/ml of pro-angiogenic factors, and a second phase including delivering a stabilization medium, e.g., having 0.5-2% of serum and 1-20 ng/ml of angiogenic factors.

Abstract: Disclosed are an artificial tissue including an artificial papillary layer, an artificial skin and a method of manufacturing the same. The artificial tissue includes an extracellular matrix layer including a first extracellular matrix and an artificial papillary layer formed on the extracellular matrix layer and including a papilla or papillae, each papilla including a cell and a second extracellular matrix, thereby overcoming the structural limitation of the flat dermis of existing artificial tissue, exhibiting excellent ability to mimic human physiology, and enabling application thereof to the production of various tissues and organs having a fine uneven structure in the human body.

Abstract: Recombinant cells and methods therefor are contemplated that allow for rapid and high titer production of recombinant viruses, and especially replication deficient Ad5 virus. In some preferred aspects, the host cell is modified to produce an inhibitor that reduces or eliminates the expression of a therapeutic protein encoded in the virus, while in other aspects, the virus includes a gene that directly or indirectly reduces or eliminates the expression of a therapeutic protein encoded in the virus. Most preferably, shRNA encoded by the host cell will reduce or suppress expression of a payload gene encoded in the recombinant virus.

Abstract: A method of non-covalently loading a plant picornavirus is described. The method includes contacting a plant picornavirus in solution with a molar excess of a cargo molecule to load the plant picornavirus with the cargo molecule, and then purifying the loaded plant picornavirus. Examples of cargo molecules include imaging agents, antitumor agents, and antiviral agents. Loaded plant picornaviruses prepared in this manner can be used to delivering cargo molecule to cells.

Abstract: Disclosed herein is an engineered bacteriophage comprising an indicator gene, wherein said indicator gene is an RNA aptamer or a green fluorescent protein (GFP) or GFP-like protein, and further wherein said indicator gene can indicate the presence of a microorganism, such as a bacterial infection. The engineered bacteriophage can be capable of infecting and killing the microorganism. The engineered microorganism can be in a composition for delivery to a subject, and can be in hyaluronic acid, for example. Also disclosed are methods of using the engineered bacteriophage to diagnose and/or treat a subject with a bacterial infection.

Abstract: Provided herein are methods and compositions for killing a target bacterium. Also disclosed are engineered bacteriophages.

Abstract: The present invention provides an ascorbate peroxidase mutant MaAPX1M36K and an application thereof, belonging to the technical field of biotechnology. An amino acid sequence of the mutant MaAPX1M36K of the present invention is shown in SEQ ID NO. 3. In the present invention, the mutant MaAPX1M36K reconstruction protein is obtained by the method of prokaryotic expression. It is found that the mutant MaAPX1M36K improves catalytic efficiency by nearly 5 times, providing a technical reference for further study and application of APX1.

Abstract: Described herein are non-natural NAD+-dependent alcohol dehydrogenases (ADHs) capable of at least two fold greater conversion of methanol or ethanol to formaldehyde or acetaldehyde, respectively, as compared to its unmodified counterpart. Nucleic acids encoding the non-natural alcohol dehydrogenases, as well as expression constructs including the nucleic acids, and engineered cells comprising the nucleic acids or expression constructs are described. Also described are engineered cells expressing a non-natural NAD+-dependent alcohol dehydrogenase, optionally include one or more additional metabolic pathway transgene(s), methanol metabolic pathway genes, target product pathway genes, cell culture compositions including the cells, methods for promoting production of the target product or intermediate thereof from the cells, compositions including the target product or intermediate, and products made from the target product or intermediate.

Abstract: Provided are compositions related to HSD17B13 variants, including isolated nucleic acids and proteins related to variants of HSD17B13, and cells comprising those nucleic acids and proteins. Also provided are methods related to HSD17B13 variants. Such methods include methods for modifying a cell through use of any combination of nuclease agents, exogenous donor sequences, transcriptional activators, transcriptional repressors, and expression vectors for expressing a recombinant HSD17B13 gene or a nucleic acid encoding an HSD17B13 protein. Also provided are therapeutic and prophylactic methods for treating a subject having or at risk of developing chronic liver disease.

Abstract: A ketoreductase mutant and use thereof are provided. The amino acid sequence of the ketoreductase mutant is an amino acid sequence obtained by mutation of the amino acid sequence shown in SEQ ID NO: 1, wherein the mutation at least comprises one of the following mutation sites: position 6, position 94, position 96, position 117, position 144, position 156, position 193, position 205, position 224, position 176, position 85 and position 108; alternatively, the amino acid sequence of the ketoreductase mutant has a mutation site in a mutated amino acid sequence and an amino acid sequence having 80% or more homology with the mutated amino acid sequence.

Abstract: The disclosure relates to the production of methyl laurate by genetically engineered photosynthetic microorganisms. In particular, provided herein are methods and compositions for producing methyl laurate from carbon dioxide and water in genetically engineered cyanobacteria and other photosynthetic microorganisms.

Abstract: A mutant PHA synthetase which enables production of a PHA copolymer with a high or low 3HH ratio while maintaining PHA productivity. The mutant PHA synthetase is a mutant polyhydroxyalkanoate synthetase having an amino acid sequence having 85% or more sequence identity with the amino acid sequence of SEQ ID NO: 1 and having at least one of the following mutations (a) to (c): (a): mutation of substitution of serine at 389th position from N-terminus of the amino acid sequence of SEQ ID NO: 1 with an amino acid other than serine; (b): mutation of substitution of leucine at 436th position from the N-terminus of the amino acid sequence of SEQ ID NO: 1 with an amino acid other than leucine; and (c): mutation of deletion of 11 or more and 19 or less amino acid residues from C-terminus of the amino acid sequence of SEQ ID NO: 1.

Abstract: Disclosed herein are compositions and methods of treating disclosure provides for compounds for use in treating Mitochondrial Neurogastrointestinal Encephalopathy Syndrome (MNGIE). In some embodiments, the compounds have cell penetrating activity and thymidine phosphorylase activity. In certain embodiments, the compounds disclosed herein comprise: a) at least one cell-penetrating peptide (CPP) moiety; and b) a thymidine phosphorylase, or an active fragment or analog thereof (TP), wherein the CPP is coupled, directly or indirectly, to TP.

Abstract: The present invention provides engineered RNA polymerase variants and compositions comprising these variants. The present invention further provides engineered T7 RNA polymerase variants and compositions comprising these variants. These variants have been evolved for selective incorporation of the m7G(5?)ppp(5?)m7G cap analog over GTP at the initiation of in vitro transcription. The present invention also provides methods for selective capping of RNA transcripts.

Abstract: The present invention provides engineered RNA polymerase variants and compositions comprising these variants. The present invention further provides engineered T7 RNA polymerase variants and compositions comprising these variants. These variants have been evolved for selective incorporation of the m7G(5?)ppp(5?)m7G cap analog over GTP at the initiation of in vitro transcription. The present invention also provides methods for selective capping of RNA transcripts.

Abstract: This disclosure relates to Cas9-nucleic acid complexes and uses related thereto. In certain embodiments, the disclosure contemplates transgenic plants and animals genetically engineered to express Cas9-nucleic acid complexes disclosed herein. In certain embodiments, the disclosure relates to methods of treating or preventing, diseases, conditions, cancer, viral infections or other pathogenic infection using vectors configured to express a Cas9-nucleic acid complex disclosed herein.

Abstract: The embodiments disclosed herein utilize fluorescence polarization based preliminary screen to identify a putative set of Cas inhibitors from an initial set of candidate inhibitors. The primary screening assay is followed by secondary screening assay to validate the putative set of inhibitors selected by the preliminary screen. In some embodiments, the present disclosure includes compositions and methods are provided for the inhibition of the function of RNA guided endonucleases, including the identification and use of such inhibitors.

Abstract: Compositions and methods for gene editing. In some embodiments, a polynucleotide encoding Cas9 is provided that can provide one or more of improved editing efficiency, reduced immunogenicity, or other benefits.

Abstract: The present disclosure provides engineered RNA-guided enzymes for editing live cells.

Abstract: Methods and constructs for RNA-guided targeting of transcriptional activators to specific genomic loci.

Abstract: Aspects of the present disclosure include glucoamylase (GA) variants having at least one improved property over a parent GA, compositions containing the GA variants, nucleic acids encoding the GA variants, and methods for producing and using the same. In some aspects, the GA variant is a variant of a parent GA from Humicola grisea.

Abstract: This invention relates to novel recombinant clostridial neurotoxins exhibiting an increased duration of effect and to methods for the manufacture of such recombinant clostridial neurotoxins. These novel recombinant clostridial neurotoxins comprise at least one domain wherein said domain comprises an amino acid sequence consisting of at least 50 amino acid residues, wherein said amino acid sequence consists of at least one proline and at least one alanine residue. The invention relates also to novel recombinant clostridial neurotoxins comprising at least one domain wherein said domain comprises an amino acid sequence consisting of at least 50 amino acid residues, wherein said domain comprises a plurality of specific amino acid repeats consisting of proline, alanine and tyrosine residues, or proline, alanine and glutamine residues, or proline, alanine and threonine residues.

Abstract: The present invention claims a novel process for the production and purification of microbial collagenase (Microbial Collagenase EC 3.4.24.3) produced by the non-pathogenic aerobic bacterium Vibrio alginolyticus chemovar. iophagus (NCIMB Number: 11038, synonym LMG 3418, hereinafter called Vibrio alginolyticus), which said process provides high production levels of collagenase with a stable, reproducible, cheap fermentation process. The collagenase produced from Vibrio alginolyticus according to the process described herein also presents a specific activity superior to that of other microbial collagenases, is stable in aqueous solution, and can be frozen without significant damage.

Abstract: Disclosed herein is one or more subtilisin variant, nucleic acid encoding same, and compositions and methods related to the production and use thereof, including one or more subtilisin variant that has improved stability compared to one or more reference subtilisin.

Abstract: Disclosed herein are methods for the treatment of traumatic brain injury by transplantation of cells descended from marrow adherent stem cells that express an exogenous Notch intracellular domain. The transplanted cells form a pathway along which endogenous neurogenic cells proliferate and migrate from the subventricular zone to the site of injury.

Abstract: Activation of stem cell activation is monitored and customized based on a patient's skin condition, including skin coloration, texture, thickness, and pigmentation. Skin properties are continuously monitored during stem cell activation, including moisture, permeability, temperature, blood circulation, conductivity, blood pressure, and metabolism. Energy used for stem cell activation can be adjusted in real-time based on changes in the patient's skin condition or properties. Monitoring stem cell activation can also include measuring a molecule that is associated with stem cell activation, skin damage, or reactive oxygen species generation.

Abstract: Novel methods for rapidly extracting genomic DNA from a broad range of microbes are provided, together with compositions for use in these methods. Methods provided herein provide for extraction of increased concentrations of gDNA from many microbial samples, as well as effective recovery of gDNA from a larger number of microbial species or isolates.

Abstract: The invention provides methods for isolating RNA from whole urine and urine fractions for the diagnosis of prostate cancer and/or benign prostate hyperplasia. An exemplary method for diagnosing prostate cancer in an individual, said method comprises: (a) determining the amount of RNA encoding one or more diagnostic genes in the soluble urine fraction of a urine sample obtained from said individual; (b) comparing the amount of said RNA to a reference value for said one or more diagnostic genes, wherein said reference value is derived from the amount of RNA encoding said one or more diagnostic genes in one or more individuals that do not have prostate cancer; and (c) diagnosing said individual as having prostate cancer when the amount of said RNA is greater than said reference value.

Abstract: A method for developing capture agents for target proteins employs a compound library to find cyclic peptide sequences that bind the target protein. The target protein is also reacted with a clickable group-provider reagent to provide the protein with clickable groups. The compounds in the library are provided with complementary clickable groups that bind the clickable group on the target protein when the peptide sequences bind the target protein. In some embodiments, the cyclic peptide sequences that bind the target protein are incorporated into constructs having one or more arms that can serve as capture agents or potential treatments against the pathogens from which the target protein is derived. Some embodiments provide pharmaceutical compositions for immunoassays, diagnostics, therapeutics or the like, that employ the constructs.

Abstract: Aspects of the disclosure relate to barcoded chimeric adeno-associated virus (AAV) capsid libraries, chimeric capsids and related recombinant AAVs (rAAVs) identified using the libraries. Specifically, the chimeric AAV capsid libraries comprise a plurality of nucleic adds encoding AAV capsid proteins, wherein each nucleic acid (i) encodes a unique AAV capsid protein having distinct polypeptide regions of greater than six amino acids in length that are derived from at least two different AAV serotypes, and (ii) comprises a unique barcode sequence. Further disclosed are methods of preparing an AAV library and identifying AAV capsids tropic for a target tissue.

Abstract: A system and method for automated single cell capture and processing is described, where the system includes a deck supporting and positioning a set of sample processing elements; a gantry for actuating tools for interactions with the set of sample processing elements supported by the deck; and a base supporting various processing subsystems and a control subsystems in communication with the processing subsystems. The system can automatically execute workflows associated with single cell processing, including mRNA capture, cDNA synthesis, protein-associated assays, and library preparation, for next generation sequencing.

Abstract: Aspects of the disclosure relate to recombinant gene editing complexes comprising a recombinant gene editing protein and guide RNA (gRNA) that specifically hybridizes to a region of a C90RF72 gene (e.g., a region flanking a G4C2 repeat or within a exonic region of the gene).

Abstract: The present application provides materials and methods for treating a patient with Usher Syndrome Type 2A, both ex vivo and in vivo; materials and methods for editing a USH2A gene in a human cell; materials and methods for editing an USH2A gene containing an IVS40 mutation; materials and methods for treating a patient with an USH2A gene containing an IVS40 mutation; and a method for deleting a sequence comprising an IVS40 mutation within a USH2A gene of a cell. The present application also provides one or more gRNAs or sgRNAs for editing an USH2A gene containing an IVS40 mutation. The present application provides a therapeutic for treating a patient with Usher Syndrome Type 2A. The present application also provides a kit for treating a patient with Usher Syndrome Type 2A.

Abstract: The present invention provides compositions and methods for down-modulating the expression and/or the immuno-suppressive activity of i) the FMRP protein, ii) an mRNA encoding the FMRP protein, and/or iii) the FMR1 gene for the treatment and/or prevention of primary cancer and/or cancer metastasis in a subject in need thereof.

Abstract: The present disclosure provides nucleic acid compositions that incorporate one or more halouracil molecules. More specifically, the present disclosure reveals that the replacement of uracil nucleotides within a microRNA nucleotide sequence with a 5-halouracil increases the ability of the micro-RNA to inhibit cancer progression and tumorigenesis. As such, the present disclosure provides various nucleic acid (e.g., microRNA) compositions having 5-halouracil molecules incorporated in their nucleic acid sequences and methods for using the same. The present disclosure further provides pharmaceutical compositions comprising the modified nucleic acid compositions, and methods for treating cancers using the same.

Abstract: The present disclosure relates to antisense oligonucleotides, which target SNCA mRNA (e.g., at an intron exon junction) in a cell, leading to reduced expression of SNCA protein. Reduction of SNCA protein expression is beneficial for the treatment of certain medical disorders, e.g., a neurological disorder.

Abstract: Provided herein, inter alia, are compounds capable of binding HSP70 (e.g. mHSP70) on a cell and internalizing into said cell. The compositions provided herein may be useful for delivering therapeutic and diagnostic agents to a cell. Further provided are pharmaceutical compositions and methods of treatment using nucleic acid compounds provided herein.

Abstract: The present disclosure concerns aptamers which specifically bind to Legionella pneumophila which can be used to detect the presence of Legionella pneumophila in a sample.

Abstract: Disclosed herein are antisense compounds and methods for decreasing SOD-1 mRNA and protein expression. Such methods, compounds, and compositions are useful to treat, prevent, or ameliorate SOD-1 associated diseases, disorders, and conditions. Such SOD-1 associated diseases include amyotrophic sclerosis (ALS).

Abstract: Control Devices are disclosed including RNA destabilizing elements (RDE), RNA control devices, and destabilizing elements (DE) combined with Chimeric Antigen Receptors (CARs) or other transgenes in eukaryotic cells. Multicistronic vectors are also disclosed for use in engineering host eukaryotic cells with the CARs and transgenes under the control of the control devices. These control devices can be used to optimize expression of CARs in the eukaryotic cells so that, for example, effector function is optimized. CARs and transgene payloads can also be engineered into eukaryotic cells so that the transgene payload is expressed and delivered after stimulation of the CAR on the eukaryotic cell.

Abstract: Control Devices are disclosed including RNA destabilizing elements (RDE), RNA control devices, and destabilizing elements (DE) combined with Chimeric Antigen Receptors (CARs) or other transgenes in eukaryotic cells. Multicistronic vectors are also disclosed for use in engineering host eukaryotic cells with the CARs and transgenes under the control of the control devices. These control devices can be used to optimize expression of CARs in the eukaryotic cells so that, for example, effector function is optimized. CARs and transgene payloads can also be engineered into eukaryotic cells so that the transgene payload is expressed and delivered after stimulation of the CAR on the eukaryotic cell.