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Titolo:
Efficacy and safety analyses of a recombinant human immunodeficiency virustype 1 derived vector system
Autore:
Chang, LJ; Urlacher, V; Iwakuma, T; Cui, Y; Zucali, J;
Indirizzi:
Unive,lorida, Gene Therapy Ctr, Dept Mol Genet & Microbiol, ARB, Gainesvill Univ Florida Gainesville FL USA 32610 Genet & Microbiol, ARB, Gainesvill Univ Florida, Inst Brain, Gainesville, FL 32610 USA Univ Florida Gainesville FL USA 32610 st Brain, Gainesville, FL 32610 USA Univ Florida, Dept Oncol, Gainesville, FL USA Univ Florida Gainesville FLUSA Florida, Dept Oncol, Gainesville, FL USA
Titolo Testata:
GENE THERAPY
fascicolo: 5, volume: 6, anno: 1999,
pagine: 715 - 728
SICI:
0969-7128(199905)6:5<715:EASAOA>2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Soggetto:
EFFICIENT GENE-TRANSFER; RETROVIRAL VECTORS; REPLICATION-COMPETENT; LENTIVIRAL VECTOR; IN-VIVO; CELLS; EXPRESSION; ENHANCER; THERAPY; TRANSDUCTION;
Keywords:
HIV; lentivirus; vector; MLV; VSV-G;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
24
Recensione:
Indirizzi per estratti:
Indirizzo: Chang, LJ Unive,lorida, Gene Therapy Ctr, Dept Mol Genet & Microbiol, ARB,Gainesvill Univ Florida Gainesville FL USA 32610 icrobiol, ARB, Gainesvill
Citazione:
L.J. Chang et al., "Efficacy and safety analyses of a recombinant human immunodeficiency virustype 1 derived vector system", GENE THER, 6(5), 1999, pp. 715-728

Abstract

Lentiviruses infect both dividing and nondividing cells. In this study we characterized a lentiviral vector system consisting of a packaging vector (pHP) and a transducing vector (pTV) derived from a recombinant human immunodeficiency virus type I (HIV-I). In pHP, the long terminal repeats (LTRs), the 5' untranslated leader and portions of env and nef genes were deleted. The leader sequence of pHP was substituted with a modified Rous sarcoma virus (RSV) 59 bp leader containing a mutated RSV gag AUG and a functional 5' splice site. The pHP construct was found to direct Gag-Pol synthesis as efficiently as wild-type HIV-1. The pTV construct contains sequences required for PNA packaging, reverse transcription and integration, but lacks viral genes. Co-transfection of pHP, pTV and a vesicular stomatitis virus G (VSV-G) envelope plasmid produced vectors at titers of 10(5)-10(6) transducing units per milliliter in 48 h. Replication-competent virus (RCV) was not detected when deletions were made in the env gene in pHP The ability of this vector system to transduce dividing and nondividing cell in vitro and in vivo was also demonstrated. Compared with a Moloney murine leukemia virus (MLV) vector the HP/TV vectors transduced human muscle-, kidney-, liver-derived cell fines and CD34(+) primary hematopoietic progenitor cells more efficiently. Although the levels of the PTV transgene expression were high soon after transduction, the expression tended to decrease with time due either to the loss of proviral DNA or to the inactivation of promoter activity, which was found to be cell type-dependent. Analyses of extrachromosomal DNA showed that the unintegrated proviral DNA of lentiviral vectors survived much longer than that of the retroviral vectors. We : demonstrate that the HP/TV vector is capable of high efficiency transduction and that long-term expression of lentiviral Vectors is dependent on target cell type, the infernal promoter and the transgene itself in the transducing vector.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 11/07/20 alle ore 20:52:39