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Titolo:
Lentiviral vector gene transfer into fetal rhesus monkeys (Macaca mulatta): Lung-targeting approaches
Autore:
Tarantal, AF; Lee, CI; Ekert, JE; McDonald, R; Kohn, DB; Plopper, CG; Case, SS; Bunnell, BA;
Indirizzi:
Univ Calif Davis, Calif Reg Primate Res Ctr, Davis, CA 95616 USA Univ Calif Davis Davis CA USA 95616 Primate Res Ctr, Davis, CA 95616 USA Univ Calif Davis, Dept Pediat, Davis, CA 95616 USA Univ Calif Davis DavisCA USA 95616 vis, Dept Pediat, Davis, CA 95616 USA Childrens Hosp Los Angeles, Div Res Immunol Bone Marrow Transplantat, Los Angeles, CA 90027 USA Childrens Hosp Los Angeles Los Angeles CA USA 90027 Angeles, CA 90027 USA Ohio State Univ, Dept Pediat, Childrens Res Inst, Columbus, OH 43205 USA Ohio State Univ Columbus OH USA 43205 ns Res Inst, Columbus, OH 43205 USA
Titolo Testata:
MOLECULAR THERAPY
fascicolo: 6, volume: 4, anno: 2001,
pagine: 614 - 621
SICI:
1525-0016(200112)4:6<614:LVGTIF>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
CYSTIC-FIBROSIS; RESPIRATORY EPITHELIUM; TRANSGENIC MICE; AMNIOTIC-FLUID; IN-VIVO; THERAPY; FASCICULARIS; CELLS; ADENOVIRUS; PROSPECTS;
Keywords:
fetal gene transfer; HIV-1-derived lentivirus; EGFP; rhesus monkey; lung;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
43
Recensione:
Indirizzi per estratti:
Indirizzo: Tarantal, AF Univ Calif Davis, Calif Reg Primate Res Ctr, Davis, CA 95616 USA Univ Calif Davis Davis CA USA 95616 Ctr, Davis, CA 95616 USA
Citazione:
A.F. Tarantal et al., "Lentiviral vector gene transfer into fetal rhesus monkeys (Macaca mulatta): Lung-targeting approaches", MOL THER, 4(6), 2001, pp. 614-621

Abstract

We previously reported the efficiency of gene transfer in fetal monkeys using retroviral vectors and an intraperitoneal (IP) approach. Here, we explored intrapulmonary administration to determine whether gene transfer can belimited to the developing lung. The HIV-1-derived lentiviral vector (VSV-Gpseudotyped; 1 x 10(7) infectious particles/fetus), using the enhanced green fluorescent protein (EGFP) as a reporter, was directly injected into fetal lung with ultrasound guidance (n = 4; 55 or 70 days gestation; term 165 /- 10 days). Fetuses were monitored sonographically, fetal/maternal blood samples collected during gestation, and four of four healthy newborns were delivered at term. All lung lobes were positive for the transgene (less than or equal to 1%) when assessed by PCR, and transgene expression was observed by direct fluorescence microscopy and flow cytometry. The results of this study show the following: (1) successful gene transfer in fetal monkeys using an intrapulmonary approach; (2) less transduction of non-pulmonary tissues with gene transfer at 70 days gestation compared with 55 days gestation or use of an IP approach; (3) that the pulmonary epithelium was EGFP-positive by immunohistochemistry; and (4) no evidence of transplacental transport of vector sequences or antibody responses in the dams. The results of these investigations indicate the efficiency of fetal gene transfer by intrapulmonary delivery, and emphasize the importance of the fetal monkey as a preclinical model system for exploring in utero genetic treatment strategies for pulmonary disorders.

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Documento generato il 28/01/20 alle ore 20:58:32