The present disclosure provides compositions and methods of restoring or enhancing visual function in an individual by administering to the individual a pharmaceutical composition comprising a recombinant adeno-associated viral (rAAV) vector having a polynucleotide sequence that encodes a medium wavelength cone opsin (MW-opsin). The MW-opsin is expressed in a retinal cell in the individual, thereby restoring or enhancing visual function.

Disclosed herein include adeno-associated virus (AAV) acoustic targeting peptides. An AAV comprising the AAV acoustic targeting peptide can exhibit increased transduction at site(s) of focused ultrasound blood-brain barrier opening (FUS-BBBO), increased neuronal tropism, and diminished transduction of peripheral organs. Disclosed herein include recombinant adeno-associated virus (rAAV) comprising an AAV acoustic targeting peptide disclosed herein. Also provided herein include methods of delivering an agent to one or more target brain region(s) of a subject.

Aspects of the disclosure relate to compositions and methods for expressing anti-Vascular endothelial cell growth factor (VEGF) agent in a cell or subject. In some embodiments, the disclosure provides rAAVs comprising a capsid protein (e.g., AAV2 variants, AAV2/3 hybrid variants, AAV8 variants, etc.), and a transgene encoding an anti-VEGF agent (e.g., KH902) and one or more regulatory sequences. In some embodiments, compositions described herein are useful for treating subjects having diseases associated with angiogenesis or aberrant VEGF activity/signaling.

A rAAV vector is described herein which has an AAVhu68 capsid and at least one expression cassette in the capsid. The at least one expression cassette comprises nucleic acid sequences encoding a functional SMN protein and expression control sequences that direct expression of the SMN sequences in a host cell. Also provided are compositions containing this rAAVhu68.SMN vector and methods of using same for spinal muscular atrophy in a patient.

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.

Provided herein are variant adeno-associated virus (AAV) capsid proteins having one or more modifications in amino acid sequence relative to a parental AAV capsid protein, which, when present in an AAV virion, confer increased infectivity of one or more types of retinal cells as compared to the infectivity of the retinal cells by an AAV virion comprising the unmodified parental AAV capsid protein. Also provided are recombinant AAV virions and pharmaceutical compositions thereof comprising a variant AAV capsid protein as described herein, methods of making these rAAV capsid proteins and virions, and methods for using these rAAV capsid proteins and virions in research and clinical practice, for example in, e.g., the delivery of nucleic acid sequences to one or more ceils of the retina for the treatment of retinal disorders and diseases.

Systems and methods to genetically modify B cells to express selected antibodies are described. The systems and methods can be used to: obviate the need for classical vaccinations; provide protection against infectious agents for which no vaccinations are currently available; provide protection against infectious agents when patients are otherwise immune-suppressed; and/or provide a benefit provided by a therapeutic antibody, such as in the treatment of autoimmune disorders.

Compositions and methods for treatment of CEP290 related diseases are disclosed.

A recombinant adeno-associated virus (rAAV) comprising an AAVhu68 capsid and a vector genome comprising a lysosomal beta-galactosidase gene (for example, galactosidase beta 1 gene, GBL1) is provided (i.e., rAAVhu68.GBL1). Also provided a composition containing an effective amount of rAAVhu68.GBL1 to ameliorate symptoms of GM1 gangliosidosis, including, e.g., increased average life span, decreased need for feeding tube, reduction in seizure incidence and frequency, reduction in progression towards neurocognitive decline and/or improvement in neurocognitive development.

The present invention relates to expression constructs and viral and other vectors for the treatment and/or prevention of chronic pain.