Gene Therapy: SUMO to the Rescue
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.
The SUMO Tag
The solution to expression
Figure 2: The rAAV payload, foreign gene, can be expressed as hSUMO-fusion that will be cleaved to generate native gene product. SUMO Protease cleaves the SUMO tag to separate the expressed gene product. hSUMOstar is engineered not to be cleaved in mammalian cells thus preserving the expression enhancing properties of SUMO. Please consult our Therapeutic Protein slide deck.
Many Advantages of hSUMO and hSUMOstar Fusion with rAAV and Gene Therapy Including:
✅ Under expressed genes are efficiently translated
✅ The gene product is stable and accumulates to increase therapeutic response.
✅ Development of potent rAAV gene reduces the amount of rAAV required for therapeutic benefit.
LifeSensors has established a Search Sheet (below) that allows you to search a variety of papers that describe the application of SUMO to express proteins in a variety of systems.