The present disclosure provides infectious recombinant adeno-associated virus (rAAV) virions that comprise a variant capsidprotein and a heterologousnucleic 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.
Isolated polynucleotide sequences exhibiting endothelial cell specific promoter activity, novel cis regulatory elements and methods of use thereof enabling treatment of diseases characterized by aberrant neovascularization or cell growth are disclosed.
ARPE-19 cells were evaluated as a platform cell line for encapsulated and unencapsulated cell-based delivery technology. ARPE-19 cells were found to be hardy (the cell line is viable under stringent conditions, such as in central nervous system or intra-ocular environment); can be genetically modified to secrete the protein of choice; have a long life span; are of human origin; have good in vivo device viability; deliver efficacious quantity of growth factor; trigger no or low level host immune reaction, and are non-tumorigenic.