VectorGen, LLC

rminants, makes a pharmacological side effects. We are proposing a completely innovative approach to gene therapy; an approach which builds on research from a number of sources. Our vector is designed to deliver its therapeutic cargo, and then conditionally repress its own replication. The therapeutic gene will be induced in the presence of "live" HIV; and will prevent the budding of HIV particles from infected cells, and destabilize the assembly of infectious HIV virions. The risk of generating a dangerous lentivirus through recombination is minimized by all but eradicating HIV sequences in the vector cargo, and by human-optimizing any sequences that overlap with the HIV genome. We plan to insert the transgene into the human genome site-specifically, to reduce the risk of oncogenic activation or other positional effects. We propose that this vector will confer lasting protection against HIV in uninfected, as well as infected individuals, after a single administration. As such, it would be a radical departure from traditional vaccine-based therapies, which have been slow to bear fruit in clinical trials. Finally, and equally important, the vector design may be used as a platform. The same auto-regulatory mechanism could be employed to combat any characterized virus.