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Titolo:
Variation in adenovirus receptor expression and adenovirus vector-mediatedtransgene expression at defined stages of the cell cycle
Autore:
Seidman, MA; Hogan, SM; Wendland, RL; Worgall, S; Crystal, RG; Leopold, PL;
Indirizzi:
Cornell Univ, Weill Med Coll, Div Pulm & Crit Care Med, New York, NY USA Cornell Univ New York NY USA Div Pulm & Crit Care Med, New York, NY USA Cornell Univ, Weill Med Coll, Inst Med Genet, New York, NY USA Cornell Univ New York NY USA Med Coll, Inst Med Genet, New York, NY USA
Titolo Testata:
MOLECULAR THERAPY
fascicolo: 1, volume: 4, anno: 2001,
pagine: 13 - 21
SICI:
1525-0016(200107)4:1<13:VIAREA>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
GENE-TRANSFER VECTORS; COOPERATIVE BINDING; AIRWAY EPITHELIUM; POLYMERASE-ALPHA; NUCLEAR IMPORT; HELA-CELLS; IN-VITRO; DNA; INFECTION; THERAPY;
Keywords:
adenovirus; coxsackie-adenovirus receptor; integrin; cell cycle; mitosis; paclitaxel; nocodazole; Taxol; cyclin;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
62
Recensione:
Indirizzi per estratti:
Indirizzo: Leopold, PL Cornell Univ, Weill Med Coll, Div Pulm & Crit Care Med, New York, NY USA Cornell Univ New York NY USA Crit Care Med, New York, NY USA
Citazione:
M.A. Seidman et al., "Variation in adenovirus receptor expression and adenovirus vector-mediatedtransgene expression at defined stages of the cell cycle", MOL THER, 4(1), 2001, pp. 13-21

Abstract

Detailed investigations have addressed the infection pathway of recombinant adenovirus (Ad) gene transfer vectors, but little attention has been paidto the influence of cell physiology on the outcome of Ad infection. Based on observations that Ad infection of clonal cell populations show cell-to-cell variability in the extent of capsid binding, we hypothesized that the cell cycle may influence the outcome of Ad infection. To address this hypothesis, we evaluated Ad association with cells in both unsynchronized and pharmacologically synchronized cell populations. In unsynchronized cell populations, elevated Ad association with cells correlated with expression of cyclin B1, a marker of entry into the M phase of mitosis. The same analysis conducted on cell populations that were synchronized at M phase (using paclitaxel or nocodazole) or at S phase (using aphidicolin) confirmed that M phase cells bound three- to sixfold more capsid compared with unsynchronized cells, which are primarily in the G(1) and G(2) phases. The elevated association of vectors with cells translated into 2.5- to 4fold greater transgene expression 24 hours after infection. Assessment of cell surface expression of Ad receptors demonstrated that both the high-affinity coxsackie-adenovirus receptor for Ad fiber protein and the low-affinity alpha (v) integrin receptor for Ad penton base protein showed increased cell surface expression at M phase (1.5-fold and 2- to 3-fold increases, respectively). These data demonstrate that Ad infection of a homogenous population of cells can vary depending on the cell cycle stage, with enhanced Ad binding and expression correlating with the enhanced expression of Ad receptors during M phase. These observations have relevance to understanding the mechanisms of gene transfer by Ad vectors and should help in the design of in vive gene transfer strategies.

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Documento generato il 29/02/20 alle ore 03:01:44