AAV9-CAG-FLPo

In the dynamic landscape of gene therapy, adeno-associated virus (AAV) has emerged as an important delivery vector, showing great potential for treating various genetic diseases. In recent years, the field has made great progress, and several AAV-based products have been approved. These products highlight the success and increasing acceptance of viral vectors as safe and effective delivery vehicles for therapeutic and vaccine genes in the clinic.

AAV has a genome of approximately 4.7 kb, containing two major open reading frames (ORFs), rep and cap, flanked by two inverted terminal repeats (ITRs). The alternative reading frame present in the cap contains aap and maap. The cap ORF also encodes three overlapping capsid viral proteins (VP) in mRNA generated by alternative splicing. The larger transcript contains the entire cap coding region and produces VP1, while the shorter transcript encodes VP2 (ACG) and VP3 (AUG) from two separate start codons. Thus, the VP1 (87 kDa) and VP2 (72 kDa) capsid proteins have the same ∼530 C-terminal amino acid sequence within VP3, but have additional amino acids at the N terminus. A total of 60 VPs assemble into a T=1 icosahedral viral capsid with a 1:1:10 ratio of VP1, VP2, and VP3, respectively, with VP3 accounting for ∼90% of the capsid.