The present invention relates to compositions and methods for the treatment of myotonic dystrophy.

Provided herein are improved, cost-effective and environmentally friendly methods of production of recombinant AAV (rAAV) in embryonated avian eggs. Further provided herein is a provides embryonated avian eggs as novel host vehicles for high-yield production of rAAV, including both packaging and propagation. In particular, embryonated chicken eggs provide a novel expression vehicle for AAV of mammalian origin, irrespective of AAV serotype. The disclosed methods may comprise packaging of rAAV in embryonated avian eggs (e.g., chicken eggs) by inoculating an embryonated avian egg with a first nucleic acid vector comprising a transgene and a second nucleic acid vector comprising AAV rep and cap genes, incubating the egg, and isolating rAAV from the egg, wherein the AAV is of non-avian origin. Also provided are methods of purifying and propagating packaged rAAV in embryonated avian eggs or in avian embryonic fibroblasts.

The present invention relates to a Crumbs homologue (CRB) therapeutic for use as a medicament or in a method of treatment or prophylaxis, for example in the treatment or prophylaxis of a retinal disorder due to mutations in the Crumbs homologue-1 (CRB1) gene, such as Leber's congenital amaurosis 8 (LCA8) or retinitis pigmentosa 12 (RP12). In particular, the present invention relates to a recombinant viral vector comprising CRB2 or modified non-toxic forms of either CRB1 or CRB3 that resemble CRB2.

Provided herein are methods and compositions for expressing Otoferlin, e.g., utilizing adeno-associated viral (AAV) particles. Further provided herein are compositions of AAV particles comprising one or more polynucleotides encoding Otoferlin are codon optimized for expression in human cells. Such methods and compositions may be useful for treatment of diseases and disorders such as Deafness, Autosomal Recessive 9 (DFNB9). Also provided are kits comprising such compositions.

Compositions and methods for delivering effector entities to the CNS of a subject are provided. Engineered AAV capsids that bind GPI-anchored proteins on the BBB are provided as well as methods for their use, including delivery of gene therapy and effector entities. Also provided, are methods for reducing the infectivity of the CNS by an AAV.

Compositions for the treatment of hemophilia B are provided. In certain embodiments, the composition is a recombinant adeno-associated virus (rAAV) comprising an AAVrh10 capsid and a vector genome packaged therein, wherein the vector genome comprises an AAV 5′ inverted terminal repeat (ITR), a coding sequence for a human Factor IX (F9) having coagulation function operably linked to regulatory elements which direct expression of the human Factor IX in liver cells, and an AAV 3′ ITR.

The invention relates to isolated nucleic acids and rAAV-based compositions, methods and kits useful for treating genetic diseases (e.g., alpha-1 antitrypsin deficiency).

The present invention relates to a Crumbs homologue (CRB) therapeutic for use as a medicament or in a method of treatment or prophylaxis, for example in the treatment or prophylaxis of a retinal disorder due to mutations in the Crumbs homologue-1 (CRB1) gene, such as Leber's congenital amaurosis 8 (LCA8) or retinitis pigmentosa 12 (RP12). In particular, the present invention relates to a recombinant viral vector comprising CRB2 or modified non-toxic forms of either CRB1 or CRB3 that resemble CRB2.

The present invention provides reagents and methods for modulating cone photoreceptor activity, and devices for assessment of cone photoreceptor activity.

The present disclosure provides the gene therapy compositions comprising vectors (e.g., viral vectors) suitable for delivery of nucleic acids encoding immunomodulatory proteins or functional fragments thereof, and methods of using the same. Certain aspects of the disclosure are directed to an adeno-viral vector (AAV) delivery of nucleic acids encoding two or more immunomodulatory proteins or functional fragments thereof to a tumor.