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Titolo:
Rhesus monkey model for fetal gene transfer: Studies with retroviral-basedvector systems
Autore:
Tarantal, AF; ORourke, JP; Case, SS; Newbound, GC; Li, J; Lee, CI; Baskin, CR; Kohn, DB; Bunnell, RA;
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 Ohio State Univ, Childrens Res Inst, Dept Pediat, Columbus, OH 43205 USA Ohio State Univ Columbus OH USA 43205 Dept Pediat, Columbus, OH 43205 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
Titolo Testata:
MOLECULAR THERAPY
fascicolo: 2, volume: 3, anno: 2001,
pagine: 128 - 138
SICI:
1525-0016(200102)3:2<128:RMMFFG>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
MACAQUE MACACA-FASCICULARIS; GREEN FLUORESCENT PROTEIN; IN-UTERO; HIGH-TITER; RECOMBINANT RETROVIRUSES; HEMATOPOIETIC-CELLS; BETA-GALACTOSIDASE; PRENATAL-DIAGNOSIS; STABLE TRANSDUCTION; LENTIVIRAL VECTORS;
Keywords:
fetal gene transfer; MLV; HIV-1-derived lentivirus; EGFP; rhesus monkey;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
65
Recensione:
Indirizzi per estratti:
Indirizzo: Tarantal, AF Univ Calif Davis, Calif Reg Primate Res Ctr, Pedrick & Hutchison Rd, Davis, CA 95616 USA Univ Calif Davis Pedrick & Hutchison Rd Davis CA USA 95616 SA
Citazione:
A.F. Tarantal et al., "Rhesus monkey model for fetal gene transfer: Studies with retroviral-basedvector systems", MOL THER, 3(2), 2001, pp. 128-138

Abstract

Many life-threatening conditions that can be diagnosed early in gestation may be treatable in utero using gene therapy. In order to determine in utero gene transfer efficiency and safety, studies were conducted with fetal rhesus monkeys as a model for the human. Included in these studies were Moloney murine leukemia virus (MLV)-based amphotropic retrovirus, vesicular stomatitis virus-G (VSV-G) pseudotyped MLV, and a VSV-C pseudotyped HIV-l-basedvector, all expressing the enhanced green fluorescent protein (EGFP) as a reporter gene and driven by a cytomegalovirus-immediate early promoter (N =16). Rhesus monkey fetuses were administered viral vector supernatant preparations by the intraperitoneal (ip) (N = 14) or intrahepatic (ih) (N = 2) routes via ultrasound guidance at 55 +/- 5 days gestation (late first trimester; term 165 +/- 10 days). Fetuses were monitored sonographically, specimens were collected prenatally and postnatally, and tissue harvests were performed at birth or 3 or 6 months postnatal age (3-10 months post-gene transfer). PCR analyses demonstrated that transduced cells were present at similar to1.2% in peripheral blood mononuclear cells from fetuses administered amphotropic MLV, <0.5% in fetuses receiving MLV/VSV-G, and <similar to>4.2% for the lentiviral vector, which decreased to 2% at birth. Hematopoietic progenitors showed that overall (mean of all time points assessed), similar to 25% of the collected colonies were positive for the EGFP transgene with the lentiviral vector, which war; significantly greater than results achieved with the MLV-based vector systems (4-9%; P less than or equal to 0.001-0.016). At necropsy, 0.001-10% of the total genomic DNA was positive for EGFPin most tissues for all groups. EGFP-positive fluorescent cells were foundin cell suspensions of thymus, liver, spleen, lymph nodes, cerebral cortex, and bone marrow (0.5-6%). Overall, the results of these studies have shown: (1) healthy infants expressing vector sequences up to 10 months post-gene transfer, (2) fetal primate administration of retroviral vectors results in gene transfer to multiple organ systems, (3) the highest level of gene transfer to hematopoietic progenitors was observed with the lentiviral vector system, and (4) there was no evidence of transplacental transfer of vector sequences into the dams. The rhesus monkey is an important preclinical primate model system for exploring gene transfer approaches for future applications in humans.

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Documento generato il 22/01/20 alle ore 09:19:41