scAAV2-CAG-GFP

AAV vectors are among the most promising viral vectors for human gene therapy. Gene transfer via AAV vectors can treat a variety of central nervous system diseases, including Parkinson's disease, Alzheimer's disease, and lysosomal storage diseases, demonstrating the potential for human gene therapy applications. Recombinant adeno-associated virus serotype 2 (AAV2), the most widely used AAV vector, can express genes in postmitotic neurons for long periods of time with minimal immune response, even after administration of high doses of virus. In addition, AAV2 vectors can be packaged with capsid proteins from different AAV serotypes. These alternative serotypes can provide unique tropisms and improve transduction efficiency depending on the region of interest and target neuronal subtype. Together, these advantages have generated great interest in AAV2 vectors as gene transfer vectors for axonal regeneration after injury.

Conventional AAV2 vectors containing single-stranded DNA must be converted to a double-stranded replicative form, which is the rate-limiting step in the AAV vector replication cycle. Double-stranded, self-complementary AAV vectors (scAAV) bypass this step, offering the opportunity to achieve more efficient transduction and faster, more sustained transgene expression. Researchers compared scAAV2 to traditional single-stranded (ss) AAV2 vectors for reporter gene expression in DRGs, and the results showed that scAAV2 transgene expression was faster and stronger than the equivalent ssAAV2 vector. For small tissues in the CNS, such as DRGs, more robust expression levels may be critical, and scAAV vectors can significantly reduce the vector load required to achieve sustained transgene expression. Using lower viral titers can also reduce the risk of adverse effects due to immune responses induced by the vector itself.