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Fig. 2 | Virology Journal

Fig. 2

From: Recent advances in various adeno-associated viruses (AAVs) as gene therapy agents in hepatocellular carcinoma

Fig. 2

Diagram of rAAv transduction pathway. Adeno-associated virus (AAV) is recognized by glycosylated cell surface receptors of the host. This triggers the internalization of the virus via clathrin-mediated endocytosis. AAV then traffics through the cytosol mediated by the cytoskeletal network. Owing to the somewhat low pH environment of the endosome, the VP1/VP2 region undergoes a conformational change. Following endosomal escape, AAV undergoes transport into the nucleus and uncoating. AAV can also undergo proteolysis by the proteasome. There are currently two classes of recombinant AAVs (rAAVs) in use: single-stranded AAV (ssAAV) and self-complementary AAV (scAAV). ssAAVs are packaged as either sense (plus-stranded) or anti-sense (minus-stranded) genomes. These single-stranded forms are still transcriptionally inert when they reach the nucleus and must be converted to double-stranded DNA as a prerequisite for transcription. This conversion can be achieved by second-strand synthesis via host cell DNA polymerases or by annealing the plus and minus strands that may coexist in the nucleus. Because scAAVs are already double-stranded by design, they can immediately undergo transcription. The viral ITRs present in the rAAV genome can drive inter-molecular or intra-molecular recombination to form circularized episomal genomes that can persist in the nucleus [16]

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