Figure 1. Adeno-associated virus variant genomes.

(A) Wild-type adeno-associated virus (AAV) genome, which consists of two inverted terminal repeats flanking coding sequences for four Rep proteins (Rep 78, Rep 68, Rep 52 and Rep 40) involved in genome replication, and four capsid proteins (VP1, VP2, AAP and VP3). (B) Recombinant AAV genome, where the coding sequences of the AAV genome are substituted with the transgenic cassette, which is flanked by the 3′ and 5′ inverted terminal repeats. Upon entry into the transduced cell (blue arrow), the single-stranded genome is converted by host factors into a transcriptionally active double-stranded form (dashed green arrow). (C) scAAV genome, in which the transgenic cassette is expressed as an inverted repeat with a deleted/mutated 3′ terminal repeats in the middle, and flanked by two intact 5′ terminal repeats. Upon entry into the transduced cell, the inverted repeats pair along their length, creating a double-stranded transcriptionally active genome, bypassing the need for second strand synthesis by host cell factors. Deletion/mutation of the 3′ terminal repeats prevents the generation of monomeric forms by the Rep endonucleases, thereby stabilizing the self-complementary AAV genome in its dimeric form.