Adeno-associated virus site-specifically integrates into a muscle-specific DNA region.
Proceedings of the National Academy of Sciences. 2000-04-11; 97(9): 4862-4866
DOI: 10.1073/pnas.080079397
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1. Proc Natl Acad Sci U S A. 2000 Apr 25;97(9):4862-6.
Adeno-associated virus site-specifically integrates into a muscle-specific DNA
region.
Dutheil N(1), Shi F, Dupressoir T, Linden RM.
Author information:
(1)Institute for Gene Therapy and Molecular Medicine, Mount Sinai School of
Medicine, New York, NY 10029, USA.
The nonpathogenic human virus adeno-associated virus type 2 (AAV) has evolved the
potentially unique strategy to establish latency by site-specifically integrating
its genome into human chromosome 19 (19q13.3-qter) at a locus designated AAVS1.
This nonhomologous, site-specific recombination of viral DNA with the human
genome provides a basis for developing targeted gene therapy vectors. To assess
whether the region surrounding AAVS1 might have contributed to the selection of
the specific integration site, we have investigated this locus. Here, we show
that AAVS1 is closely linked to the slow skeletal troponin T gene, TNNT1, which
has been mapped previously to 19q13.4. In support of this idea, we demonstrate
that site-specific AAV DNA integration can result in the formation of TNNT1-AAV
junctions. The question now arises whether muscle represents a natural target
tissue for latent AAV infection. This possibility is of additional interest in
view of recent observations that muscle tissue is particularly well suited for
AAV-mediated gene transfer. The question also occurs whether latent infection by
AAV can lead to phenotypic changes of the multinucleated muscle fiber cells.
DOI: 10.1073/pnas.080079397
PMCID: PMC18323
PMID: 10758163 [Indexed for MEDLINE]