Gene Therapy and SUMO
Recombinant adeno associated viruses (rAAV) have become the vehicle of choice to deliver gene therapy for cure genetically inherited diseases but also gene delivery system for many chronic diseases. There are major hurdles in production of safe rAAV. Generally, rAAV is produced by transfecting three plasmid systems: (1) an AAV2 ITR-containing plasmid carrying the gene of interest; (2), a plasmid that carries the AAV2 Rep-Cap proteins; and (3), a plasmid that provides the helper genes isolated from adenovirus. This method of producing therapeutic dose of rAAV is very labor intensive and expensive due to low yield of the rAAV. While progress is being made to manufacture large titers of therapeutic viruses, it is hampered by lack of foreign gene expression or degradation of the targeted protein (step 1). If we can construct a highly potent rAAV that expresses the therapeutic gene, it will solve the problem of large manufacturing batches, decreasing the cost of goods. We believe application of SUMO (Small Ubiquitin-Like Modifiers) fusion with therapeutic gene will solve many of the problems described above.