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Titolo:
SITES OF RECOMBINANT ADENOASSOCIATED VIRUS INTEGRATION
Autore:
RIVADENEIRA ED; POPESCU NC; ZIMONJIC DB; CHENG GS; NELSON PJ; ROSS MD; DIPAOLO JA; KLOTMAN ME;
Indirizzi:
MT SINAI SCH MED,1 GUSTAVE L LEVY PL NEW YORK NY 10029 NIH,TUMOR CELL BIOL LAB BETHESDA MD 20892 NIH,BIOL LAB BETHESDA MD 20892
Titolo Testata:
International journal of oncology
fascicolo: 4, volume: 12, anno: 1998,
pagine: 805 - 810
SICI:
1019-6439(1998)12:4<805:SORAVI>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
ADENOASSOCIATED VIRUS; TARGETED INTEGRATION; DIRECT VISUALIZATION; NEOMYCIN RESISTANCE; VIRAL INTEGRATION; MAMMALIAN-CELLS; DETROIT-6 CELLS; FRAGILE SITES; CELLULAR DNA; VECTOR;
Keywords:
GENE THERAPY; AAVS1; FLUORESCENT CHROMOSOME IN SITU; HYBRIDIZATION; PARVOVIRUS; INSERTIONAL MUTAGENESIS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
33
Recensione:
Indirizzi per estratti:
Citazione:
E.D. Rivadeneira et al., "SITES OF RECOMBINANT ADENOASSOCIATED VIRUS INTEGRATION", International journal of oncology, 12(4), 1998, pp. 805-810

Abstract

Adeno-associated virus (AAV), a defective parvovirus, is considered apromising vector for the delivery of therapeutic genes to cells. Bothwild-type and recombinant AAV display a wide tropism and integrate into the host genome, in the absence of helper virus, establishing a latent infection. A unique characteristic of wild-type AAV and a potential advantage for use as a delivery system for gene therapy is the site-specific integration of wild-type virus within a small region of chromosome 19, 19q13.3-qter (AAVS1), in up to 85% of cell lines infected with the virus. Although recombinant AAVs, containing only the inverted terminal repeats of wild-type virus, can integrate efficiently into the host genome, specificity for the AAVS1 site appears to be lost. To address this question, the integration characteristics of two recombinant AAVs lacking the rep and cap genes in HeLa cells were examined. Analysis of Southern blots indicated that none of twenty-six cell clones generated after infection with either one of the recombinant AAVs demonstrated integration within the AAVS1 locus on chromosome 19. Analysisof five of the cell lines by fluorescent chromosome in situ hybridization confirmed the loss of chromosome 19 specificity. Each integrationsite mapped near a known fragile site and/or location of a proto-oncogene or growth regulatory gene. Retention of site-specific integrationof wild-type AAV will require the inclusion of additional AAV-specific sequences within the recombinant vectors.

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Documento generato il 05/04/20 alle ore 09:19:50