Abstract: The present disclosure provides a modified AAV capsid protein comprising a targeting peptide, optionally further comprising a liver-toggle mutation. The modified AAV capsid protein can form an rAAV, which has a preferred tropism, specificity or biodistribution in vivo or in vitro. The rAAV of the present disclosure can be used for gene therapies targeted at a specific tissue. The present disclosure also provides rAAV compositions comprising MTM1 coding sequences and their use to treat subjects suffering from X-linked myotubular myopathy (XLMTM).

Abstract: This disclosure describes compositions and methods for altering the bio-distribution of adeno-associated viruses (AAVs) in subjects.

Abstract: The invention relates to methods of culturing cells, generating cell lines, and delivering polynucleotides to cells involving the use of HDAC inhibitors and/or adeno-associated virus (AAV) rep proteins.

Abstract: This disclosure provides compositions and methods for altering or changing the tissue tropism, e.g., liver tropism, of adeno-associated viruses (AAV).

Abstract: The disclosure pertains to a recombinant adeno-associated virus (rAAV) comprising an Anc80L65 capsid for delivering a polynucleotide (e.g., a transgene) into the central nervous system (CNS). Further provided includes methods for treating CNS diseases using the rAAV and pharmaceutical compositions comprising the rAAV.

Abstract: This disclosure describes compositions and methods for altering the bio-distribution of adeno-associated viruses (AAVs) in subjects.

Abstract: The invention provides improved gene therapy methods and compositions. In particular embodiments, gene therapies comprise hematopoietic stem and progenitor cell compositions with increased therapeutic efficacy and methods of making and using the same. In other particular embodiments, the present invention contemplates compositions and methods for increasing transduction efficiency and vector copy number (VCN) of human hematopoietic stem and progenitor cells (HSPCs) to yield improved gene therapy compositions. In various embodiments, the present invention contemplates, in part, a population of HSPCs transduced with a lentiviral vector. In various embodiments, the present invention contemplates a method of treating sickle cell disease in a subject comprising administering the subject an effective amount of the population of hematopoietic cells contemplated herein.

Abstract: This invention provides a variety of novel adeno-associated vims (AAV) vectors for gene therapy applications in the treatment of glycogen storage disease type 1a (GSD-Ia). Disclosed herein are a number of recombinant nucleic acid molecules, vectors and recombinant AAV that incorporate a modified G6PC promoter/enhancer sequence. Utilization of the modified G6PC promoter/enhancer sequence results in enhanced AAV yield and quality when expressed from various host cell platforms. Also provided herein are compositions comprising the novel AAV of the invention and methods of treating GSD-Ia using the same.

Abstract: The invention relates to methods of culturing cells, generating cell lines, and delivering polynucleotides to cells involving the use of HDAC inhibitors and/or adeno-associated virus (AAV) rep proteins.

Abstract: The invention provides improved gene therapy methods and compositions. In particular embodiments, gene therapies comprise hematopoietic stem and progenitor cell compositions with increased therapeutic efficacy and methods of making and using the same. In other particular embodiments, the present invention contemplates compositions and methods for increasing transduction efficiency and vector copy number (VCN) of human hematopoietic stem and progenitor cells (HSPCs) to yield improved gene therapy compositions. In various embodiments, the present invention contemplates, in part, a population of HSPCs transduced with a lentiviral vector. In various embodiments, the present invention contemplates a method of treating sickle cell disease in a subject comprising administering the subject an effective amount of the population of hematopoietic cells contemplated herein.