Abstract: Fibronectin type III (FN3) domain antibodies, polynucleotides capable of encoding the FN3 domain antibodies or antigen-binding fragments, cells expressing FN3 domain antibodies or antigen-binding fragments, as well as associated vectors and detectably labeled FN3 domain antibodies or antigen-binding fragments may be used to engineer FN3 domain-targeting chimeric antigen receptors (CARs). Methods of making the FN3 domain antibodies, CARs, and engineered immune cells, and methods of using the engineered immune cells are applicable to treat diseases including cancer.

Abstract: Induced pluripotent stem cells (iPSCs) derived from a T cell of a T cell subset. T cells derived from iPSCs derived from a T cell. Methods of deriving iPSCs from a T cell. Methods of deriving T cells from iPSCs including deriving a T cell of a T cell subset from an iPSC. Methods of engineering chimeric antigen receptor (CAR)-expressing or T cell receptor (TCR)-expressing iPSC. Methods of administering T cells derived using the methods disclosed. Induced pluripotent stem cell lines derived from T cells, methods of deriving induced pluripotent stem cell lines, and methods of deriving T cells from induced pluripotent stem cell lines.

Abstract: Some embodiments of the present disclosure relate to one or more compositions that upregulate the production of one or more sequences of mRNA. The sequences of mRNA may encode for translation of a target biomolecule, thereby causing an increase in bioavailability of the target biomolecule within a subject that is administered the one or more compositions. In some embodiments of the present disclosure, the target biomolecule is a fusion protein with an Fc fragment, such as a mu opioid receptor-Fc (MOR-Fc) that may be biologically active in the absence of an opioid ligand.

Abstract: A method for cloning a full length coding sequence for a light chain of a rabbit monoclonal antibody is provided. In some embodiments, this method may involve: fusing a B cell from a rabbit having a B4 allotype with a 240E cell or a derivative thereof to produce a hybridoma, wherein the B cell and the hybridoma produce a monoclonal antibody; making cDNA from the hybridoma; amplifying from the cDNA a full length coding sequence for the light chain of a monoclonal antibody produced by the hybridoma using: a forward primer that hybridizes to a site in SEQ ID NO: 10, and a reverse primer having a 3? end of sequence CTARCAGTCX (SEQ ID NO: 11), wherein R is A or G and X is A, AC, ACC or ACCC; and cloning the amplified sequence into an expression vector to produce a first plasmid.

Abstract: The present disclosure provides methods for genetically modifying lymphocytes and methods for performing adoptive cellular therapy that include transducing T cells and/or NK cells. The methods can include inhibitory RNA molecule(s) and/or engineered signaling polypeptides that can include a lymphoproliferative element, and/or a chimeric antigen receptor (CAR), for example a microenvironment restricted biologic CAR (MRB-CAR). Additional elements of such engineered signaling polypeptides are provided herein, such as those that drive proliferation and regulatory elements therefor, as well as replication incompetent recombinant retroviral particles and packaging cell lines and methods of making the same. Numerous elements and methods for regulating transduced and/or genetically modified T cells and/or NK cells are provided, such as, for example, those including riboswitches, MRB-CARs, recognition domains, and/or pH-modulating agents.

Abstract: An artificial non-coding RNA (ncRNA) module constructed by a synthetic biology technique and the use of the artificial ncRNA module in the construction of an artificial nitrogen fixation system are disclosed. The RNA module can enhance the post-transcriptional stability of nifHDK mRNA by interacting with a nitrogenase coding gene nifHDK mRNA, thereby improving the nitrogen fixation ability of a chassis microorganism. A fusion expression vector carrying the artificial RNA module is constructed and transformed into different chassis nitrogen-fixing microorganisms. It is confirmed through experiments that, under nitrogen fixation conditions, the artificial RNA module of the present disclosure can significantly improve the nitrogenase activity of a recombinant engineering bacterial strain.

Abstract: The invention provides for delivery, engineering and optimization of systems, methods and compositions for manipulation of sequences and/or activities of target sequences. Provided are delivery systems and tissues or organ which are targeted as sites for delivery. Also provided are vectors and vector systems some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing CRISPR complex formation in eukaryotic cells to ensure enhanced specificity for target recognition and avoidance of toxicity and to edit or modify a target site in a genomic locus of interest to alter or improve the status of a disease or a condition.

Abstract: The present invention relates to Adeno-associated virus type 9 methods and materials useful for intrathecal delivery of polynucleotides. Use of the methods and materials is indicated, for example, for treatment of lower motor neuron diseases such as SMA and ALS as well as Pompe disease and lysosomal storage disorders. It is disclosed that administration of a non-ionic, low-os-molar contrast agent, together with a rAA9 vector for the expression of Survival Motor Neuron protein, improves the survival of SMN mutant mice as compared to the administration of the expression vector alone.

Abstract: Systems and methods are provided for transfecting cells, such as mammalian cells and nonmammalian cells, using an electroporation apparatus having an electroporation chamber including a first electrode, a second electrode and a path defined in the electroporation chamber. The electroporation apparatus includes a first input allowing passage of cells and cargo into the electroporation chamber and a first output allowing passage of electroporated cells from the electroporation chamber.

Abstract: The present invention is directed to Saccharomyces-generated extracellular vesicles (EVs) comprising a foreign RNA molecule or protein and at least one foreign membrane surface exposed ligand that specifically binds to a target receptor displayed on a target cell. The present invention also relates to methods of making and using these Saccharomyces-generated EVs for targeted gene silencing. The present invention also relates to fusion proteins comprising a Saccharomyces extracellular vesicle anchor protein and a second peptide designed to bind to cell-specific receptors.

Abstract: There is described a vector for treating a ciliopathy such as Bardet-Biedl syndrome, wherein the vector comprises a promoter operably linked to a ciliopathy gene, wherein the vector can provide transduction of the ciliopathy gene into multiple organs, wherein the promoter is a ubiquitous promoter which can provide expression of the ciliopathy gene in the transduced organs, and wherein the ciliopathy gene encodes a functional protein corresponding to the protein that is mutated in the ciliopathy. Also described is the use of the above vector in a method of treating a ciliopathy, the method comprising administering a therapeutically effective amount of the vector to a patient suffering from a ciliopathy.

Abstract: Blood from a blood source is drawn into a fluid flow circuit. A mononuclear cell product is separated from the blood, followed by at least a portion of the mononuclear cell product being conveyed into an electroporation device without disconnecting the blood source from the fluid flow circuit. The electroporation device opens pores in a membrane of at least one of the cells of the mononuclear cell product to allow DNA material (which is added to the mononuclear cell product prior to electroporation) to enter and modify the genome of the cell. At least a portion of the modified mononuclear cell product is returned to the blood source. The mononuclear cell product may be washed prior to being conveyed into the electroporation device. The modified mononuclear cell product may be washed after exiting the electroporation device.

Abstract: The present disclosure provides adeno-associated virus (AAV) vectors, comprising coevolved capsid variant proteins, pharmaceutical compositions, methods of making, and methods for delivering such to a subject.

Abstract: Use of a transforming growth factor beta (TGF-?) signalling inhibitor for producing a population of brown adipocytes in vitro.

Abstract: The invention is related to an oncolytic adenovirus that comprises a sequence encoding a hyaluronidase enzyme inserted in its genome. This adenovirus spreads more efficiently in the tumour mass and therefore the oncolytic effect is increased. Injecting the oncolytic adenovirus of the invention endovenously, tumour volume regressions are obtained. Therefore the oncolytic adenovirus of the present invention is useful for the treatment of a cancer or a pre-malignant state of cancer.

Abstract: The present disclosure provides recombinant adeno-associated virus (rAAV) virions with an engineered capsid protein identified using a high-throughput sequencing screen or rational design. In particular, the disclosure provides AAV5 virions and capsid proteins with increased transduction efficiency in cardiac cells, increased cell-type selectivity, and/or other desirable properties.

Abstract: Nucleic acid immunization is achieved by delivering a nucleic acid (NA), e.g., a mRNA or a DNA, encapsulated within a lipid-NA nanoparticle. The NA encodes an immunogenic compound of interest. The lipid-NA nanoparticle is effective for in vivo delivery of NA to a vertebrate cell, including upon administration to a subject. The lipid-NA nanoparticle are incorporated in pharmaceutical compositions for immunizing subjects against various diseases.

Abstract: Provided herein are recombinant adeno-associated virus (rAAV) compositions that can restore phenylalanine hydroxylase (PAH) gene function in cells, and methods for using the same to treat diseases associated with reduction of PAH gene function (e.g., PKU). Also provided are nucleic acids, vectors, packaging systems, and methods for making the adeno-associated virus compositions.

Abstract: Provided herein are adeno-associated virus (AAV) compositions that can express a phenylalanine hydroxylase (PAH) polypeptide in a cell, thereby restoring the PAH gene function. Also provided are methods of use of the AAV compositions, and packaging systems for making the AAV compositions.

Abstract: The present invention provides polynucleotide vectors for high expression of heterologous genes. Some vectors further comprise novel transposons and transposases that further improve expression. Further disclosed are vectors that can be used in a gene transfer system for stably introducing nucleic acids into the DNA of a cell. The gene transfer systems can be used in methods, for example, gene expression, bioprocessing, gene therapy, insertional mutagenesis, or gene discovery.