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Titolo:
Factors affecting long-term expression of a secreted transgene product after intravenous administration of a retroviral vector
Autore:
McCormack, JE; Edwards, W; Sensintaffer, J; Lillegren, L; Kozloski, M; Brumm, D; Karavodin, L; Jolly, DJ; Greengard, J;
Indirizzi:
Chiron Corp, Ctr Gene Therapy, San Diego, CA 92121 USA Chiron Corp San Diego CA USA 92121 Gene Therapy, San Diego, CA 92121 USA
Titolo Testata:
MOLECULAR THERAPY
fascicolo: 4, volume: 3, anno: 2001,
pagine: 516 - 525
SICI:
1525-0016(200104)3:4<516:FALEOA>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
MEDIATED GENE-TRANSFER; IN-VIVO; FACTOR-VIII; ADENOVIRAL VECTORS; HEMOPHILIA-A; IMMUNE-RESPONSES; MOUSE-LIVER; RAT-LIVER; THERAPY; MICE;
Keywords:
retroviral vector; intravenous; growth hormone; long-term expression;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
53
Recensione:
Indirizzi per estratti:
Indirizzo: Jolly, DJ Advantagene Inc, Sunset Dr, Encinitas, CA 92024 USA Advantagene Inc Sunset Dr Encinitas CA USA 92024 s, CA 92024 USA
Citazione:
J.E. McCormack et al., "Factors affecting long-term expression of a secreted transgene product after intravenous administration of a retroviral vector", MOL THER, 3(4), 2001, pp. 516-525

Abstract

We have studied parameters affecting in vivo expression of human growth hormone (hGH) in mice after intravenous administration of a retroviral vectorencoding the protein as a model system for clotting factor VIII gene therapy. Such treatment results in a brief burst of high-level expression followed by lower level sustained expression of the hGH in the circulation. The major targets for transduction in the mouse are liver and spleen. Such direct transduction (i.e., without surgical or chemical induction of cell division) requires vector at high titer (greater than or equal to 10(8) cfu/ml) and is dose dependent. Transduction efficiency decreases with increasing ageof the recipient. Nevertheless, longterm expression in adults is observed after administration of vector as a split dose on 2 consecutive days. We also show that anti-vector immune responses may enhance long-term expression and that both anti-vector and anti-transgene immunity can be modulated. This work provides a framework for the rational development of means to enhance the efficiency of retroviral vectors for use in clinical gene replacementtherapy.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 19/02/20 alle ore 14:54:33