Wagner, Ralf and Graf, Marcus and Bieler, Kurt and Wolf, Hans and Grunwald, Thomas and Foley, Paul and Ueberla, Klaus (2000) Rev-independent expression of synthetic gag-pol genes of human immunodeficiency virus type 1 and simian immunodeficiency virus: Implications for the safety of lentiviral vectors. HUMAN GENE THERAPY, 11 (17). pp. 2403-2413. ISSN 1043-0342
Full text not available from this repository. (Request a copy)Abstract
The safety of lentiviral vectors for clinical applications is still a major concern. The gag-pol expression plasmids and the lentiviral vectors used in previous studies contain homologous regions, which constitute a risk for recombination events. Synthetic gag-pol genes of human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) were therefore constructed, in which the codon usage was optimized for expression in human cells without altering the amino acid sequences. The synthetic gag-pol genes allowed efficient expression of these genes in the absence of Rev and the 5' untranslated leader region. Both the HIV-1 and the SIV synthetic gag-pol expression plasmids could mediate transduction of an SIV vector into nondividing human cells with titers of about 10(6) transducing units/ml. Similar titers were obtained with a four-plasmid vector-packaging system based on HIV-1. Using a biological assay, homologous recombination events between the synthetic gag-pol expression plasmids and an SIV vector were undetectable and in comparison with a previously used gag-pol expression plasmid at least approximately 100-fold less frequent. By eliminating regions of homology and sequences involved in packaging, synthetic gag-pol genes should improve the safety profile of lentiviral vectors.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NONDIVIDING CELLS; IN-VIVO; EFFICIENT TRANSDUCTION; STABLE TRANSDUCTION; HIV-1 INFECTION; T-LYMPHOCYTES; DELIVERY; TRANSCRIPTION; REQUIREMENTS; REPLICATION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 21 Mar 2022 06:43 |
| Last Modified: | 21 Mar 2022 06:43 |
| URI: | https://pred.uni-regensburg.de/id/eprint/42090 |
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