Aav vectors for retinal and cns gene therapy

A method to treat an ocular disorder in an individual comprising delivery of a composition comprising a rAAV particle to the retina of an individual, wherein the rAAV particles comprise

• a) a rAAV capsid comprising an AAV2 capsid protein comprising one or more amino acid substitutions at one or more positions R484, R487, K527, K532, and/or R588, numbering based on VP1 numbering of AAV2,
• wherein the one or more amino acid substitutions is with a hydrophobic amino acid residue,
• wherein the one or more amino acid substitutions reduces binding of the rAAV particle to a heparin sulfate proteoglycan, and
• b) a rAAV vector comprising a heterologous nucleic acid and at least one AAV terminal repeat.

A method for delivering a heterologous nucleic acid to the eye of an individual comprising administering a recombinant adeno-associated virus (rAAV) particle to the subretina of the individual, wherein the rAAV particle comprises

• a) a rAAV capsid comprising AAVrh8R capsid proteins comprising one or more amino acid substitutions at one or more positions R485, R488, K528, and/or R533, numbering based on VP1 numbering of AAVrh8R,
• wherein the one or more amino acid substitutions is with a hydrophobic amino acid residue, and
• wherein the one or more amino acid substitutions reduces binding of the rAAV particle to a heparin sulfate proteoglycan. and
• b) a rAAV vector comprising the heterologous nucleic acid and at least one AAV inverted terminal repeat.

A method for delivering a heterologous nucleic acid to the central nervous system (CNS) of an individual comprising administering a recombinant adeno-associated virus (rAAV) particle to the CNS of the individual, wherein the rAAV particle comprises

• a) a rAAV capsid comprising AAV2 capsid proteins comprising one or more amino acid substitutions at one or more positions R484, R487, K527, K532, and/or R588, numbering based on VP1 numbering of AAV2,
• wherein the one or more amino acid substitutions is with a hydrophobic amino acid residue;
• and
• b) a rAAV vector comprising the heterologous nucleic acid and at least one AAV inverted terminal repeat.