2003
DOI: 10.1073/pnas.0937739100
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Adeno-associated viruses undergo substantial evolution in primates during natural infections

Abstract: Adeno-associated viruses (AAVs) are single-stranded DNA viruses that are endemic in human populations without known clinical sequelae and are being evaluated as vectors for human gene therapy. To better understand the biology of this virus, we examined a number of nonhuman primate species for the presence of previously uncharacterized AAVs and characterized their structure and distribution. AAV genomes were widely disseminated throughout multiple tissues of a variety of nonhuman primate species. Surprising div… Show more

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Cited by 294 publications
(247 citation statements)
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“…AAV serotypes 1-8 share about 60% amino-acid capsid homology, [18][19][20][21][22] the largest amino-acid variations being concentrated to the hypervariable regions exposed on the capsid surface. 23 Variation in capsid structure affects viral tropism and expression kinetics in terms of the onset and expression levels of therapeutic genes, and the use of different serotypes may allow for a more cellspecific gene transfer. 3,6,8,12,24,25 Robust photoreceptor transduction has been reported after subretinal injection of many vector types; however, photoreceptors are only infrequently transduced after intravitreal injection of the serotypes tested to date.…”
Section: Introductionmentioning
confidence: 99%
“…AAV serotypes 1-8 share about 60% amino-acid capsid homology, [18][19][20][21][22] the largest amino-acid variations being concentrated to the hypervariable regions exposed on the capsid surface. 23 Variation in capsid structure affects viral tropism and expression kinetics in terms of the onset and expression levels of therapeutic genes, and the use of different serotypes may allow for a more cellspecific gene transfer. 3,6,8,12,24,25 Robust photoreceptor transduction has been reported after subretinal injection of many vector types; however, photoreceptors are only infrequently transduced after intravitreal injection of the serotypes tested to date.…”
Section: Introductionmentioning
confidence: 99%
“…AAVs are single-stranded DNA viruses (members of the Parvovirus family) that are naturally detected but non-pathogenic in humans. [22][23][24][25][26] The various AAV serotypes have been expanded to include 4120 genomes. 27 AAVs have been considered promising for gene therapies of cardiovascular diseases because some AAV serotypes (AAV1, 6 and 9) have high tropism for cardiomyocytes and ensure a stable long-term transgene expression through site-specific genomic integration for wild-type AAVs.…”
Section: Developments In Vehicles and Gene Delivery Techniques For Mymentioning
confidence: 99%
“…A long-term follow-up will however be required to confirm these usual safety issues. [22][23][24][25][26] There are, however, some potential disadvantages with AAVs including the slow kinetics of expression, the limited packaging capability (o4.8 kb) and the natural presence of serotype-specific neutralizing antibodies in 20-40% of the human population. 28 Recent advances in AAV engineering have provided specific solutions to these issues.…”
Section: Developments In Vehicles and Gene Delivery Techniques For Mymentioning
confidence: 99%
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“…Over 40 genomic variants having been reported. 2 It appears that there are several major clades of related variants. Within these clades, many other individual variants appear to have been generated by recombination within the capsid coding sequence between different parental serotypes.…”
Section: Many New Aav Serotypes Have Been Discoveredmentioning
confidence: 99%