Team:Heidelberg/Project/Capsid Shuffling


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Capsid Shuffling

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Adeno-associated viruses (AAVs) are a class of single stranded DNA viruses that are not able to replicate without a helper virus. This makes them a perfect tool for the iGEM community, as no special safety requirements have to be fulfilled to work with a non-replication virus, because it is non-pathogenic. Because of their wide range of tropism they are used for transgene delivery in a variety of gene therapeutic approaches.

In the class of AAVs, there are several serotypes that have been isolated from humans or non-human primates, the first and most well-known of them being AAV2. AAV serotypes are defined as naturally evolved variants of AAV that do not react to the same antibodies. All serotypes show different tissue specificites when injected into mouse or humans, and this tissue tropism is thought to be mainly due to interactions between the virus capsid and receptors on the cell surface.

Most AAVs exhibit a rather broad tropism, AAV2 and AAV9 for example have been shown to transducer liver, muscle, lung and nervous system. Other serotypes, for example AAV1 and AAV7, can infect very rapidly or more efficiently than others (reviewed in Wu et al., 2006). Although divers, not one of the AAVs would make a good gene delivery shuttle by itself. Various approaches have been undertaken to change or combine AAVs in order to alter their tropism or transduction efficiency. These approaches mostly target the capsid genes by rationally creating AAV hybrids with certain properties or fusing targeting ligands to the proteins (reviewed in Gao et al., 2005).

Another fundamental drawback of wild type AAVs for applicability in gene therapy is their high abundance in nature. It has been estimated that up to 80% of humans are immune against AAV2, which has a potentially fatal impact on clinical studies using AAV2 (Moskalenko et al., 2000).