AAV9-CAG-iCre

Due to their proven safety and success rates in clinical trials over the years, transgene-carrying adeno-associated viruses (AAVs) have become an important tool in gene therapy to correct genetic defects that lead to mutations or ineffective protein expression or to enhance existing low levels of protein expression. Recombinant AAV (rAAV) vectors are currently being considered for a variety of non-traditional uses, such as gene knockout, genome editing or modification, and non-coding RNA modulation. The success of rAAV vectors carrying transgenes depends on a number of factors, including adequate transduction of target tissues and sustained protein expression levels in target tissues. For recombinant AAV (rAAV) vectors, transgene genomes up to 5 kb in size can be packaged into capsids. rAAV can be produced by transient transfection of HEK293 cells, baculovirus/Sf9 cell systems, herpes simplex virus type 1 systems, or other systems using different packaging and production cell lines. VP monomers assemble the AAV T=1 icosahedral capsid using monomer-monomer interactions associated with 2-, 3-, and 5-fold symmetries. The capsid surface topology exhibits a depression at the 2-fold, three protrusions at the 3-fold, and a cylindrical channel flanked by depressions at the 5-fold. In addition, there is a region between the 2-fold and 5-fold depressions, termed the 2/5-fold wall. Although all AAV serotypes share these major capsid features, differences in amino acid residues and loop conformations result in different receptor usage, tissue tropism, transduction efficiency, and antigenic reactivity. These amino acid differences are primarily located in surface loops, particularly in the previously described variable regions (VRs). When the VP structures of AAV serotypes are superimposed, these VRs are structurally defined as two or more amino acids with Cα positions greater than 1 Å apart.