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Titolo:
Targeted gene transfer to lymphocytes using murine leukaemia virus vectorspseudotyped with spleen necrosis virus envelope proteins
Autore:
Engelstadter, M; Buchholz, CJ; Bobkova, M; Steidl, S; Merget-Millitzer, H; Willemsen, RA; Stitz, J; Cichutek, K;
Indirizzi:
Paul Ehrlich Inst, Dept Med Biotechnol, D-63225 Langen, Germany Paul Ehrlich Inst Langen Germany D-63225 echnol, D-63225 Langen, Germany Dr Daniel Den Hoed Canc Ctr, Dept Clin & Tumor Immunol, Rotterdam, Netherlands Dr Daniel Den Hoed Canc Ctr Rotterdam Netherlands otterdam, Netherlands
Titolo Testata:
GENE THERAPY
fascicolo: 15, volume: 8, anno: 2001,
pagine: 1202 - 1206
SICI:
0969-7128(200108)8:15<1202:TGTTLU>2.0.ZU;2-D
Fonte:
ISI
Lingua:
ENG
Soggetto:
SINGLE-CHAIN ANTIBODIES; RETROVIRAL VECTORS; LEUKEMIA-VIRUS; CD4-EXPRESSING CELLS; HUMAN SERUM; IN-VIVO; DISPLAY; INACTIVATION; RESISTANT; GLYCOPROTEINS;
Keywords:
retroviral vector; targeting; T cells; pseudotyping; gene therapy;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
26
Recensione:
Indirizzi per estratti:
Indirizzo: Cichutek, K Paul Ehrlich Inst, Dept Med Biotechnol, Paul Ehrlich Str 51-59, D-63225 Langen, Germany Paul Ehrlich Inst Paul Ehrlich Str 51-59 Langen Germany D-63225
Citazione:
M. Engelstadter et al., "Targeted gene transfer to lymphocytes using murine leukaemia virus vectorspseudotyped with spleen necrosis virus envelope proteins", GENE THER, 8(15), 2001, pp. 1202-1206

Abstract

In contrast to murine leukaemia virus (MLV)-derived vector systems, vectorparticles derived from the avian spleen necrosis virus (SNV) have been successfully targeted to subsets of human cells by envelope modification with antibody fragments (scFv). However, an in vivo application of the SNV vector system in gene transfer protocols is hampered by its lack of resistance against human complement. To overcome this limitation we established pseudotyping of MLV vector particles produced in human packaging cell lines with the SNV envelope (Env) protein. Three variants of SNV Env proteins differingin the length of their cytoplasmic domains were all efficiently incorporated into MLV core particles. These pseudotype particles infected the SNV permissive cell line D17 at titers of up to 10(5) IU/ml. A stable packaging cell line (MS4) of human origin released MLV(SNV) pseudoype vectors that wereresistant against human complement inactivation. To redirect their tropismto human T cells, MS4 cells were transfected with the expression gene encoding the scFv 7A5 in fusion with the transmembrane domain (TM) of the SNV Env protein, previously shown to retarget SNV vector particles to human lymphocytes. MLV(SNV-7A5)-vector particles released from these cells were selectively infectious for human T cell lines. The data provide a proof of principle for targeting MLV-derived vectors to subpopulations of human cells through pseudotyping with SNV targeting envelopes.

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Documento generato il 05/04/20 alle ore 09:20:15