scAAV1-Cre

Adeno-associated virus (AAV) is a single-stranded DNA parvovirus that relies on adenoviral co-infection for viral propagation. At least 11 naturally occurring AAV serotypes have been described. The single-stranded DNA genome size of AAV is approximately 4.7 kb long. Following administration of single-stranded recombinant AAV vectors, host cell-mediated synthesis of the second DNA strand constitutes the rate-limiting step for transgene expression efficiency and initiation. This shortcoming can be addressed by generating self-complementary AAV (scAAV) vectors that package a double-stranded genome that is half the size of the wild-type AAV genome.

scAAV vectors can be generated by deleting the terminal resolution site from one of the AAV terminal repeats, thereby preventing replication initiation at the mutant end. These constructs generate a single-stranded, inverted repeat genome with a wild-type terminal repeat at each end and a mutant terminal repeat in the middle. After capsid disassembly, the genome folds by intramolecular base pairing within the mutant terminal repeats to form a double-stranded DNA molecule. These scAAV vectors have half the transgene capacity of single-stranded AAV but are more efficient than single-stranded AAV in transducing various tissues such as muscle, liver, and brain, and reach peak expression levels more quickly than single-stranded AAV.