The technology described herein provides variant adeno-associated viral capsid polypeptides and viruses comprising the same. Further provided herein are methods for delivering a viral payload using viruses comprising variant capsid polypeptides described herein. Described herein are viral vectors comprising a variant sequence of the capsid gene, VP1. In particular, viral vectors with capsid polypeptide mutations that modify tropism of the viral particles relative to particles with wild-type capsid polypeptide are described.

The present invention relates to synthetic retinal ON-bipolar cell-specific promoter sequences and their use in therapeutic transgene delivery to the eye for the improvement and/or restoration of vision. The invention features metabotropic glutamate receptor 6 (mGluR6) promoters for an increased and more specific expression in ON-bipolar cells, in particular in cone ON-bipolar cells of the human macula.

The present invention relates to transcription regulatory elements (TREs) such as promoters, which may be used to express a transgene within a cell such as a mammalian cell. The invention further relates to polynucleotides and vectors comprising such transcription regulatory elements, which may be operably linked to a transgene, as well as methods of gene therapy based on using such vectors.

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.

A vaccine including a vector and a transgene is provided. The transgene encodes a plurality of peptides and is packaged in the vector, in which the peptides in order include a secretion signal peptide, at least one tumor antigen, at least one co-inhibitory peptide and a toll-like receptor 9 (TLR9) antagonist.

Disclosed herein are peptide sequences capable of directing adeno-associated viruses (AAV) to target specific environments, for example the nervous system and the heart, in a subject. Also disclosed are AAVs having non-naturally occurring capsid proteins comprising the disclosed peptide sequences, and methods of using the AAVs to treat diseases.

The present disclosure provides a variant AAV capsid protein that confers tropism to lung cells and recombinant adeno-associated viruses comprising the variant AAV and pharmaceutical compositions comprising same and their use in the delivery of heterologous nucleic acids to lung cells for the treatment of pulmonary disorders.

Provided herein are compositions and methods for regenerating retinal ganglion cells (RGCs) from retinal neuron cells by activating transcription factors such as one or more of Atoh7, Brn3B, Sox4, Sox11, or Ils1. The retinal neuron cells may be interneuron cells such as amacrine cells, horizontal cells, and bipolar cell. The regenerated RGCs can project axons into discrete subcortical brain regions and establish retina-brain connections. They can respond to visual stimulation and transmit electrical signals into the brain. Therefore, the regenerated RGCs can replace damaged or degenerated RGCs, thereby treating vision impairment or blindness. The methods are likewise applicable to degenerated, damaged, or aged RGCs to stimulate them to regrow functional axons, thereby rejuvenating these RGCs.

The disclosure provides compositions and methods for the preparation, manufacture and therapeutic use of viral vectors, such as adeno-associated virus (AAV) particles having viral genomes encoding one or more antibodies or antibody fragments or antibody-like polypeptides, for the prevention and/or treatment of diseases and/or disorders.

The present disclosure provides infectious recombinant adeno-associated virus (rAAV) virions that comprise a variant capsid protein and a heterologous nucleic acid. The present disclosure further provides the variant adeno-associated virus (AAV) capsid proteins (and/or a nucleic acid encoding the variant AAV capsid proteins), which confer to an infectious rAAV virion an increased resistance to human AAV neutralizing antibodies. The present disclosure further provides host cells comprising an infectious rAAV virion and/or a nucleic acid encoding a subject variant AAV capsid protein. The present disclosure further provides methods of delivering a heterologous nucleic acid to a target cell where the target cell is contacted with a subject infectious rAAV virion. The present disclosure further provides methods of delivering a gene product to an individual, the methods generally involving administering an effective amount of a subject rAAV virion to an individual in need thereof.