scAAV9-CAG-GFP

Self-complementary adeno-associated virus serotype 9 (scAAV9) combines the unique tissue tropism of AAV9 with the enhanced expression kinetics of a self-complementary DNA structure. As an engineered variant of natural AAV9, this vector system overcomes key limitations of traditional single-stranded AAV (ssAAV), eliminating the need for second-strand DNA synthesis in target cells—a rate-limiting step that delays transgene expression. The packaging mechanism of the scAAV9 vector involves the insertion of an inverted repeat sequence, which forms an intramolecular double-stranded DNA structure after uncoating. This innovative design allows the therapeutic gene to be transcribed immediately, without waiting for host cell polymerases to synthesize the complementary strand, resulting in faster and more efficient transgene expression compared to ssAAV vectors. Studies have shown that scAAV9 can achieve therapeutic protein levels within 24-48 hours after administration, while traditional ssAAV requires 1-2 weeks.

Serotype 9 was chosen as the capsid platform due to its superior biodistribution characteristics, including efficient crossing of the blood-brain barrier and broad tropism for central nervous system tissues, myocardium, liver, and skeletal muscle. scAAV9 combines these natural targeting capabilities while overcoming the previous limitations of delayed expression associated with AAV9. This makes it particularly important in treating acute diseases requiring rapid therapeutic effects. Furthermore, the vector efficiently and durably transduces non-dividing cells, making it an ideal choice for long-term correction of genetic defects. Currently, scAAV9 is being applied in multiple disease areas, achieving significant success in clinical trials for spinal muscular atrophy and experimental treatments for neurodegenerative diseases such as Batten disease.