AAV-2 as a gene therapy vector targeting the blood brain barrier (BBB)

The blood-brain barrier, which excludes the entry of therapeutic drugs from blood to brain, is a major hurdle for the treatment of neurological diseases. In order to overcome it, we adopt a direct targeting method by modifying AAV-2 virus capsid. Neurotropic viruses can cross the BBB to infect brains cell. A short 29-amino acid long peptide derived from rabies virus glycoprotein (RVG) has been shown to enable transvascular delivery of small interfering RNA to the central nervous system by specifically interacting with the nicotinic acetylcholine receptor (AchR) on neuronal cells (Kumar, 2007). In our research we have three short term goals.

1. Identifying susceptible residue(s) for RVG insertions on AAV-2 capsid.
2. Production and purification of AAV2-RVG virus.
3. Examination of AAV2-RVG specificity for murine and human neuronal cells.

So far, we have identified residues that can tolerate RVG insertion to some extent and focus on production and purification of AAV2-RVG virus. At the same time, we are testing AAV2-RVG virus for its receptor specificity using various neuronal cell lines.