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

The invention provides compositions and methods useful for the treatment and prevention of conditions associated with short telomere length.

Disclosed are a composition and method of treating or preventing cardiomyopathy in a human subject. In some embodiments, the method comprises delivering a therapeutic dose of a gene therapy vector to cardiomyocytes of the human subject, wherein the gene therapy vector comprises a nucleic acid sequence encoding for PKP2.

Provided are variant adeno-associated virus (AAV) capsid proteins and recombinant AAV virions having one or more variant AAV capsid proteins. Also provided are compositions and methods for the use of the recombinant AAV virions, such as for the treatment or prophylaxis of a disease or disorder.

RNAs, such as miRNA and siRNA, and their use in treating complement-mediated disorders, are described.

Disclosed herein are novel variants of KCVN2 and their use, for example, in methods of treating a subject with a retinal disorder, such as CDSRR.

This invention relates to polynucleotides comprising a nucleotide sequence encoding a PPT1 polypeptide or a fragment thereof, vectors (viral or non-viral vectors) comprising the same, and methods of using the same for delivery of the open reading frame to a cell or a subject and to treat infantile neuronal lipofuscinosis (infantile Batten disease). The polynucleotides comprise an optimized CLN1 open reading frame.

The present disclosure provides, among other things, a recombinant adeno-associated virus (rAAV) vector comprising an AAV8 capsid and a codon-optimized sequence encoding a human phenylalanine hydroxylase (PAH) enzyme. The disclosure also provides a method of treating a subject having phenylketonuria (PKU), comprising administering to the subject in need thereof a recombinant adeno-associated vims (rAAV) vector comprising an AAV8 capsid, and a promoter operably linked to a nucleic acid sequence that encodes PAH, and wherein administering results in a decrease in phenylalanine level in the subject.

Compositions and methods for treating neurofibromatic disorders are provided herein, such as expressing Merlin protein or a functional fragment thereof from a viral vector.

Recombinant adeno associated viral vectors are disclosed. These include AAV8 or AAV9 derived vectors that include capsid proteins with mutations that confer upon the vector particular characteristics such as the ability to transduce or avoid (detarget) particular tissues, to be retained longer in the blood, or to be internalized in a cell without viral expression.