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Huelsmann, P.M.* ; Hofmann, A.D.* ; Knoepfel, S.A.* ; Popp, J.* ; Rauch, P.* ; di Giallonardo, F.* ; Danke, C.* ; Gueckel, E.* ; Schambach, A.* ; Wolff, H. ; Metzner, K.J.* ; Berens, C.*

A suicide gene approach using the human pro-apoptotic protein tBid inhibits HIV-1 replication.

BMC Biotechnol. 11:4 (2011)
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Open Access Gold
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BACKGROUND: Regulated expression of suicide genes is a powerful tool to eliminate specific subsets of cells and will find widespread usage in both basic and applied science. A promising example is the specific elimination of human immunodeficiency virus type 1 (HIV-1) infected cells by LTR-driven suicide genes. The success of this approach, however, depends on a fast and effective suicide gene, which is expressed exclusively in HIV-1 infected cells. These preconditions have not yet been completely fulfilled and, thus, success of suicide approaches has been limited so far. We tested truncated Bid (tBid), a human pro-apoptotic protein that induces apoptosis very rapidly and efficiently, as suicide gene for gene therapy against HIV-1 infection. RESULTS: When tBid was introduced into the HIV-1 LTR-based, Tat- and Rev-dependent transgene expression vector pLRed(INS)2R, very efficient induction of apoptosis was observed within 24 hours, but only in the presence of both HIV-1 regulatory proteins Tat and Rev. Induction of apoptosis was not observed in their absence. Cells containing this vector rapidly died when transfected with plasmids containing full-length viral genomic DNA, completely eliminating the chance for HIV-1 replication. Viral replication was also strongly reduced when cells were infected with HIV-1 particles. CONCLUSIONS: This suicide vector has the potential to establish a safe and effective gene therapy approach to exclusively eliminate HIV-1 infected cells before infectious virus particles are released.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Immunodeficiency-virus type-1; Programmed cell-death; Antiretroviral therapy; Dependent expression; Messenger-RNA; Cytochrome-C; Rev protein; Apoptosis; Infection; Kinetics
e-ISSN 1472-6750
Zeitschrift BMC Biotechnology
Quellenangaben Band: 11, Heft: , Seiten: , Artikelnummer: 4 Supplement: ,
Verlag BioMed Central
Begutachtungsstatus Peer reviewed