Provided are an AAV capsid protein mutant and an encoding nucleic acid, and a corresponding vector and a host cell thereof. Also provided are an adeno-associated virus vector containing the AAV capsid protein mutant, a recombinant adeno-associated virus particle constructed therefrom and carrying a gene expression cassette, a preparation method therefor, and the use thereof in treating diseases.

The present application relates to the fields of genetics, gene therapy, and molecular biology. More specifically, the present invention relates to an isolated codon-optimized nucleic acid that encodes the SMN1 protein (survival motor neuron protein), an expression cassette and a vector based thereon, as well as an AAV9 (adeno-associated virus serotype 9)-based recombinant virus for increasing the expression of the SMN1 gene in target cells, and use thereof.

A pharmaceutical composition formulated for delivery of a recombinant adeno-associated virus (rAAV) vector comprising an AAV capsid and a vector genome having human galactosylceramidase (GALC) coding sequence is provided. Also provided are 5 methods and uses of a pharmaceutical composition comprising a rAAV for the treatment of Krabbe disease.

A recombinant adeno-associated virus (rAAV) comprising an AAV capsid and a vector genome comprising a frataxin gene is provided. Also provided is a composition containing an effective amount of rAAV to ameliorate symptoms of Freidreich’s ataxia, including, e.g., reduction in progression towards neurocognitive decline and/or cardiomyopathy.

Provided herein, in some aspects, are compositions and methods for treating Barth syndrome (BTHS) using human tafazzin gene therapy or enzyme replacement therapy. The present disclosure, in some aspects, provides compositions and methods (e.g., gene therapy or enzyme replacement therapy) for treating Barth syndrome (BTHS). It was demonstrated herein that certain human Tafazzin (hTAZ) isoforms and the full length protein, as well as nucleic acids encoding them, are effective in treating BTHS.

This invention relates to modified parvovirus inverted terminal repeats (ITRs) that do not functionally interact with wild-type large Rep proteins, synthetic Rep proteins that functionally interact with the modified ITRs, and methods of using the same for delivery of nucleic acids to a cell or a subject. The modifications provide a novel Rep-ITR interaction that limits vector mobilization, increasing the safety of viral vectors.

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.

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

The invention relates to novel adeno-associated virus (AAV) capsid proteins, AAV particles comprising a novel capsid protein, polynucleotides encoding these capsid proteins and AAV vectors expressing these capsid proteins. The invention also relates to methods of making the herein described AAV vectors expressing the novel capsid proteins of the invention and associated therapeutic uses of thereof.

The disclosure relates to pharmaceutical compositions and methods of using pharmaceutical compositions comprising effective dosages of an adenoviral-based biological delivery and expression system for use in the treatment or prevention of osteoarthritis in human or mammalian joints by long-term inducible gene expression of human or mammalian interleukin-1 receptor antagonist (IL-1Ra) in synovial cells, comprising a helper-dependent adenoviral vector containing a nucleic acid sequence encoding for human or mammalian interleukin-1 receptor antagonist (IL-1Ra), left and right inverted terminal repeats (L ITR and R ITR), the adenoviral packaging signal and non-viral, non-coding stuffer nucleic acid sequences, wherein the expression of the human or mammalian interleukin-1 receptor antagonist (IL-1Ra) gene within synovial cells is regulated by an inflammation-sensitive promoter.