Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Locus control region of the human CD2 gene in a lentivirus vector confers position-independent transgene expression
Autore:
Kowolik, CM; Hu, J; Yee, JK;
Indirizzi:
City Hope Natl Med Ctr, Beckman Res Inst, Dept Virol, Duarte, CA 91010 USACity Hope Natl Med Ctr Duarte CA USA 91010 pt Virol, Duarte, CA 91010 USA
Titolo Testata:
JOURNAL OF VIROLOGY
fascicolo: 10, volume: 75, anno: 2001,
pagine: 4641 - 4648
SICI:
0022-538X(200105)75:10<4641:LCROTH>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN BETA-GLOBIN; HUMAN-IMMUNODEFICIENCY-VIRUS; MURINE LEUKEMIA-VIRUS; RETROVIRAL VECTORS; HEMATOPOIETIC-CELLS; NONDIVIDING CELLS; HIGH-LEVEL; IN-VIVO; ERYTHROLEUKEMIA-CELLS; STABLE TRANSDUCTION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
54
Recensione:
Indirizzi per estratti:
Indirizzo: Yee, JK City Hope Natl Med Ctr, Beckman Res Inst, Dept Virol, Miller Bldg 110,1500E Duarte Rd, Duarte, CA 91010 USA City Hope Natl Med Ctr Miller Bldg 110,1500 E Duarte Rd Duarte CA USA 91010
Citazione:
C.M. Kowolik et al., "Locus control region of the human CD2 gene in a lentivirus vector confers position-independent transgene expression", J VIROLOGY, 75(10), 2001, pp. 4641-4648

Abstract

Vectors derived from murine leukemia virus (MLV) have been used in many human gene therapy clinical trials. However, insertion of the locus control regions (LCRs) derived from the beta -globin gene locus or the CD2 gene intoMLV vectors frequently led to vector rearrangement. Since the human immunodeficiency virus (HIV) sequence diverges significantly from the MLV sequence, we tested whether the LCR sequence is more stable in the context of an HIV vector. Clones derived from human fibrosarcoma line HT1080 cells transduced with an HIV vector containing the T-cell-specific CD2 LCR exhibit the same wide range of transgene expression as clones lacking the LCR. In contrast, Jurkat and primary T-cell clones derived from the transduction of the LCR-containing vector show, on average, a three- to fourfold increase in transgene expression relative to that of the central vector. This is consistent with previous observiations that the CD2 LCR contains a T-cell-specific enhancer. In addition, the clones derived from the LCR-containing vector have a much lower clonal variation in transgene expression than those derived from the control vector. We also demonstrate that the level of transgene expression is proportional to the vector copy number. These results suggest that the human CD2 LCR sequence is compatible with HIV vector sequences and confers enhanced integration site-independent and copy number dependent expression of the transgene, Thus, HIV vectors may represent the ideal vehicleto deliver genes controlled by various cis-acting elements such as LCRs.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 14/07/20 alle ore 11:06:05