Abstract: The disclosure relates, in some aspects, to compositions and methods for enhanced delivery of a transgene to the central nervous system (CNS) of a subject. In some embodiments, the transgene is delivered by recombinant AAV (rAAV). In some embodiments, the method of enhancing transgene delivery comprises administering a blood brain barrier (BBB)-crossing molecule (e.g., K16ApoE) and an rAAV comprising a transgene to a subject.

Abstract: In some aspects, the disclosure relates to compositions and methods of engineering a transgene. In some embodiments, the disclosure provides self-regulating recombinant nucleic acids, viral vectors and pharmaceutical compositions comprising a MeCP2 transgene. In some embodiments, compositions and methods described by the disclosure are useful for treating diseases and disorders associated with a loss of function mutation, for example Rett syndrome.

Abstract: The disclosure relates, in some aspects, to compositions and methods for enhanced delivery of a transgene to the central nervous system (CNS) of a subject. In some embodiments, the transgene is delivered by recombinant AAV (rAAV). In some embodiments, the method of enhancing transgene delivery comprises administering a blood brain barrier (BBB)-crossing molecule (e.g., K16ApoE) and an rAAV comprising a transgene to a subject.

Abstract: In some aspects, the disclosure relates to recombinant adeno-associated viruses (rAAVs) comprising a nucleic acid encoding a fusion protein comprising a DNA-binding domain and a transcriptional regulator domain and methods of using the same. In some embodiments, expression of the fusion protein results in modified expression of a target gene in a cell.

Abstract: In some aspects, the disclosure relates to compositions and methods of engineering a transgene. In some embodiments, the disclosure provides self-regulating recombinant nucleic acids, viral vectors and pharmaceutical compositions comprising a MeCP2 transgene. In some embodiments, compositions and methods described by the disclosure are useful for treating diseases and disorders associated with a loss of function mutation, for example Rett syndrome.

Abstract: The disclosure relates, in some aspects, to adeno-associated virus capsid proteins isolated from an in vivo library and recombinant adeno-associated viruses (rAAVs) comprising the same. In some aspects, the disclosure relates to isolated nucleic acids encoding AAV capsid proteins isolated from an in vivo library. In some embodiments, rAAVs and compositions described by the disclosure are useful for delivery of one or more transgenes to the muscle-tissue of a subject.

Abstract: Aspects of the disclosure relate to compositions and methods of treating certain genetic disease (e.g., Neurofibromatosis type I) by delivering functional neurofibromin 1(NF1) protein (e.g., mini-NF1 protein and/or full-length NF1 protein) to target cell (e.g., cells and/or tissue of a subject). The disclosure is based, in part, on isolated nucleic acids (e.g., rAAV vectors) and rAAVs engineered to express a functional NF1 protein (e.g., mini-NF1 protein and/or full-length NF1 protein) or variants thereof.

Abstract: The disclosure relates, in some aspects, to adeno-associated vims capsid proteins isolated from an in vivo library and recombinant adeno-associated viruses (rAAVs) comprising the same. In some aspects, the disclosure relates to isolated nucleic acids encoding AAV capsid proteins isolated from an in vivo library. In some embodiments, rAAVs and compositions described by the disclosure are useful for delivery of one or more transgenes to the muscle-tissue of a subject.

Abstract: Aspects of the disclosure relate to compositions and methods of treating certain genetic disease (e.g., Neurofibromatosis type I) by delivering functional neurofibromin 1 (NF1) protein (e.g., mini-NF1 protein and/or full-length NF1 protein) to target cell (e.g., cells and/or tissue of a subject). The disclosure is based, in part, on isolated nucleic acids (e.g., rAAV vectors) and rAAVs engineered to express a functional NF1 protein (e.g., mini-NF1 protein and/or full-length NF1 protein) or variants thereof.

Abstract: In some aspects, the disclosure relates to recombinant adeno-associated viruses (rAAVs) comprising a nucleic acid encoding a fusion protein comprising a DNA-binding domain and a transcriptional regulator domain and methods of using the same. In some embodiments, expression of the fusion protein results in modified expression of a target gene in a cell.

Abstract: Aspects of the disclosure relate to compositions and methods of treating certain genetic disease (e.g., Neurofibromatosis type I) by delivering functional neurofibromin 1 (NF1) protein (e.g., mini-NF1 protein and/or full-length NF1 protein) to target cell (e.g., cells and/or tissue of a subject). The disclosure is based, in part, on isolated nucleic acids (e.g., rAAV vectors) and rAAVs engineered to express a functional NF1 protein (e.g., mini-NF1 protein and/or full-length NF1 protein) or variants thereof.

Abstract: Aspects of the invention relate to recombinant adeno-associated viruses (rAAVs). In some aspects, the rAAVs comprise artificial genetic regulatory elements that modulate transgene expression. In some aspects, the disclosure relates to the treatment of lysosomal storage disorders.

Abstract: Aspects of the disclosure relate to compositions and methods for the treatment of lysosomal storage disorders, such as GM1 gangliosidosis, Tay Sachs disease, and Sandhoff disease. In some embodiments, the compositions comprise viral vectors encoding beta-galactosidase. In some embodiments, the compositions comprise viral vectors encoding beta-hexosaminidase subunits (e.g. HEXA, HEXB, or combinations thereof).

Abstract: The disclosure in some aspects relates to recombinant adeno-associated viruses having distinct tissue targeting capabilities. In some aspects, the disclosure relates to gene transfer methods using the recombinant adeno-associated viruses. In some aspects, the disclosure relates to isolated AAV capsid proteins and isolated nucleic acids encoding the same.

Abstract: The disclosure relates, in some aspects, to adeno-associated vims capsid proteins isolated from an in vivo library and recombinant adeno-associated viruses (rAAVs) comprising the same. In some aspects, the disclosure relates to isolated nucleic acids encoding AAV capsid proteins isolated from an in vivo library. In some embodiments, rAAVs and compositions described by the disclosure are useful for delivery of one or more transgenes to the muscle-tissue of a subject.

Abstract: Aspects of the disclosure relate to methods for co-administration of recombinant AAVs (rAAVs). In some embodiments, the methods comprise administering one or more rAAVs engineered to express a transgene encoding ?-galactosidase (GLB1), Cathepsin A (CTSA), and/or ?-galactosidase (GLB1) and Cathepsin A (CTSA). In some embodiments, the disclosure provides methods for treating lysosomal storage disorders, such as GM-1 gangliosidosis, using compositions described by the disclosure.

Abstract: Aspects of the invention relate to recombinant adeno-associated viruses (rAAVs). In some aspects, the rAAVs comprise artificial genetic regulatory elements that modulate transgene expression. In some aspects, the disclosure relates to the treatment of lysosomal storage disorders.

Abstract: The disclosure in some aspects relates to recombinant adeno-associated viruses having distinct tissue targeting capabilities. In some aspects, the disclosure relates to gene transfer methods using the recombinant adeno-associated viruses. In some aspects, the disclosure relates to isolated AAV capsid proteins and isolated nucleic acids encoding the same.

Abstract: Aspects of the disclosure relate to bicistronic AAV nucleic acid constructs comprising a transgene encoding hexosaminidase A (HEXA) and hexosaminidase (HERB) proteins. In some embodiments, the disclosure provides methods for treating or preventing lysosomal storage disorders, such as Tay-Sachs disease and Sandhoff disease, using bicistronic nucleic acid constructs described by the disclosure.

Abstract: Disclosed are compositions, vectors, and methods for treating and preventing rabies lyssavirus infection in a subject in need thereof, including rabies lyssavirus encephalitis. The disclosed compositions relate to anti-rabies immunoglobulins and vectors for expressing anti-rabies immunoglobulins such as adeno-associated virus (AAV) vectors that express anti-rabies immunoglobulins in a subject in need thereof. In some embodiments, the disclosed methods relate to treating and/or preventing an infection by rabies lyssavirus in a subject in need thereof, the methods comprising administering to the subject a dose of an adeno-associated virus (AAV) vector that expresses an immunoglobulin that binds and neutralizes rabies lyssavirus in the subject.