The present disclosure provides a variant AAV capsid protein that confers tropism to lung cells and recombinant adeno-associated viruses comprising the variant AAV and pharmaceutical compositions comprising same and their use in the delivery of heterologous nucleic acids to lung cells for the treatment of pulmonary disorders.

The invention provides for recombinant AAV vectors comprising a miniaturized human micro-dystrophin gene and methods of using the recombinant vectors to reduce or prevent fibrosis in subjects suffering from muscular dystrophy.

There is described a nucleic acid molecule comprising a nucleotide sequence encoding a functional dystrophin protein. Also described is a vector, a host cell and a pharmaceutical composition comprising the nucleic acid molecule; use of the nucleic acid molecule in therapy, such as in the treatment of a muscular dystrophy; and a method of treating muscular dystrophy, the method comprising administering a therapeutically effective amount of the nucleic acid molecule to a patient suffering from a muscular dystrophy.

The disclosure relates to methods and compositions for regulating expression of DUX4. In some aspects, methods described by the disclosure are useful for treating a disease associated with aberrant DUX4 expression (e.g., facioscapulohumeral muscular dystrophy. FSHD).

The present invention relates to a novel approach for treating coronavirus infections, particularly infections caused by MERS-CoV, SARS-CoV and SARS-CoV-2 variants. Based on effectively targeting and cleaving single stranded RNA viruses, the present invention provides Cas13d guide RNAs, to guide the Cas13d protein to a target site in the genome of humanized Coronaviridae that is conserved between MERS-CoV, SARS-CoV and SARS-CoV-2. The disclosed invention further provides an AAV vector comprising such a Cas13d guide RNA expression cassette as well as a Cas13d for treating coronavirus infections, especially COVID-19 infections.

The present disclosure provides compositions and methods for minimally invasive optogenetic stimulation. More particularly, the present disclosure provides compositions and methods for using an ultra-sensitive step-function opsin for minimally invasive optogenetic stimulation.

Disclosed herein are compositions comprising recombinant adeno-associated virus (rAAV), as well as recombinant baculovirus systems and methods of using the same for producing and purifying such compositions. Also disclosed herein are assays for testing the titer and potency of such compositions.

Methods are described for predicting ancestral sequences for viruses or portions thereof. Also described are predicted ancestral sequences for adeno-associated virus (AAV) capsid polypeptides. The disclosure also provides methods of gene transfer and methods of vaccinating subjects by administering a target antigen operably linked to the AAV capsid polypeptides.

Recombinant adeno-associated viral (AAV) capsid proteins are provided. Methods for generating the recombinant adeno-associated viral capsid proteins and a library from which the capsids are selected are also provided.

Aspects of the disclosure relate to compositions and methods useful for treating Huntington's disease. In some embodiments, the disclosure provides interfering nucleic acids (e.g., artificial miRNAs) targeting the huntingtin gene (HTT) and methods of treating Huntington's disease using the same.