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| title | chunk | source | category | tags | date_saved | instance |
|---|---|---|---|---|---|---|
| Adeno-associated virus | 5/5 | https://en.wikipedia.org/wiki/Adeno-associated_virus | reference | science, encyclopedia | 2026-05-05T14:17:29.244416+00:00 | kb-cron |
attachment to the cell membrane receptor-mediated endocytosis endosomal trafficking escape from the late endosome or lysosome translocation to the nucleus uncoating formation of double-stranded DNA replicative form of the AAV genome expression of rep genes genome replication expression of cap genes, synthesis of progeny ssDNA particles assembly of complete virions, and release from the infected cell. Some of these steps may look different in various types of cells, which, in part, contributes to the defined and quite limited native tropism of AAV. Replication of the virus can also vary in one cell type, depending on the cell's current cell cycle phase. The characteristic feature of the adeno-associated virus is a deficiency in replication and thus its inability to multiply in unaffected cells. Adeno-associated virus spreads by co-infecting a cell with a helper virus. The first helper virus that was described as providing successful generation of new AAV particles, was the adenovirus, from which the AAV name originated. It was then shown that AAV replication can be facilitated by selected proteins derived from the adenovirus genome, by other viruses such as HSV or vaccinia, or by genotoxic agents, such as UV irradiation or hydroxyurea. Depending on the presence or absence of a helper virus, the life cycle of AAV follows either a lytic or lysogenic pathway, respectively. If there is a helper virus, AAV's gene expression activates, allowing the virus to replicate using the host cell's polymerase. When the helper virus kills the host cell, the new AAV virions are released. If there is not a helper virus present, AAV exhibits lysogenic behavior. When AAV infects a cell alone, its gene expression is repressed (AAV does not replicate), and its genome is incorporated into the host genome (into human chromosome 19). In rare cases, lysis can occur without a helper virus, but usually AAV cannot replicate and kill a cell on its own. The minimal set of the adenoviral genes required for efficient generation, of progeny AAV particles, was discovered by Matsushita, Ellinger et al. This discovery allowed for new production methods of recombinant AAV, which do not require adenoviral co-infection of the AAV-producing cells. In the absence of helper virus or genotoxic factors, AAV DNA can either integrate into the host genome or persist in episomal form. In the former case integration is mediated by Rep78 and Rep68 proteins and requires the presence of ITRs flanking the region being integrated. In mice, the AAV genome has been observed persisting for long periods of time in quiescent tissues, such as skeletal muscles, in episomal form (a circular head-to-tail conformation).
== See also ==
Isogenic human disease models Oncolytic AAV Recombinant AAV mediated genome engineering
== References ==
== External links == Kimball JW (17 May 2015). "Gene Therapy II". Kimball's Biology Pages. Archived from the original on 18 March 2005. Retrieved 13 May 2005. "Adeno-associated virus". NCBI Taxonomy Browser. 272636.