AAV1-Syn-iCre

Adeno-associated virus is a non-pathogenic, dependent parvovirus that requires the helper functions of a member of the adenovirus or herpesvirus family for efficient replication. The viral capsid is non-enveloped and therefore directly mediates many critical host-vector interactions. To date, more than 100 human and non-human primate AAVs have been identified, including 12 serotypes, whose capsid amino acid sequences have identities ranging from 51% to 99%, but relatively few have been extensively studied in the context of gene transfer. Atomic structures of different AAV serotypes solved by X-ray crystallography or cryo-electron microscopy have shown that most sequence variation is localized to surface-exposed regions of the capsid, which are most susceptible to host-vector interactions.

The wild-type AAV genome consists of a linear single-stranded DNA (ssDNA) molecule of approximately 4.7 kilobases, which includes the coding sequences for the Rep and Cap proteins, flanked by inverted terminal repeats (ITRs). Both the sense and antisense ssDNA strands are packaged into separate virions with equal efficiency. The four Rep proteins expressed through alternative promoters and splice variants are essential for genome replication, transcription, integration, and encapsidation. The three structural capsid proteins assemble into a 60-subunit icosahedral capsid in a VP1:VP2:VP3 ratio of 1:1:10 with the help of the essential assembly activating protein (AAP) expressed from open reading frame 2 of the AAV cap gene. Following infection in the absence of a helper virus, the dsDNA genome (or provirus) remains in a circular episomal form or in an integrated state, preferentially at the AAVS1 locus in human cells, until subsequently rescued upon helper virus co-infection.