Potent Inhibition of Human Immunodeficiency Virus Type 1 Replication by Conditionally Replicating Human Immunodeficiency Virus-Based Lentiviral Vectors Expressing Envelope Antisense mRNA
- 20 September 2000
- journal article
- research article
- Published by Mary Ann Liebert Inc in Human Gene Therapy
- Vol. 11 (14) , 2025-2037
- https://doi.org/10.1089/10430340050143444
Abstract
We describe an HIV-based lentiviral vector that expresses a 1-kb antisense mRNA directed against the HIV1 mRNAs containing env sequences. The expression of antisense env mRNAs (envAS) does not inhibit the synthesis of p24 expressed from the HIV-1 helper plasmid used to package the vector, as this helper has a deletion in the env gene. This allows the production of high-titer VSV-G pseudotyped lentiviral particles. In challenge experiments using unselected populations of SupT1 cells transduced with this vector, a complete inhibition of HIV-1 replication was observed for long periods of in vitro culture, even at high HIV-1 infectious doses. The potent inhibition of HIV-1 replication by this vector correlated with a low occurrence of mobilization of the vector to previously untransduced cells. The infectivity of the wild-type HIV-1 that escapes inhibition was highly inhibited, suggesting that the vector is providing HIV-1 inhibition of replication not only due to its antisense effect but also by competing for encapsidation and mobilization to noninfected cells.Keywords
This publication has 39 references indexed in Scilit:
- Modified Human Immunodeficiency Virus-Based Lentiviral Vectors Display Decreased Sensitivity toTrans-Dominant RevHuman Gene Therapy, 2000
- Inhibition of Human Immunodeficiency Virus Type 1 by Tat/Rev-Regulated Expression of Cytosine Deaminase, Interferon alpha2, or Diphtheria Toxin Compared with Inhibition by Transdominant RevHuman Gene Therapy, 1999
- Gene therapy targeting cord blood-derived CD34+ cells from HIV-exposed infants: preclinical studiesGene Therapy, 1998
- Gene Therapy for AIDS Using Retroviral Mediated Gene Transfer to Deliver HIV-1 Antisense TAR and Transdominant Rev Protein Genes to Syngeneic Lymphocytes in HIV-1 Infected Identical Twins. National Institutes of Health, Bethesda, MarylandHuman Gene Therapy, 1996
- In Vivo Gene Delivery and Stable Transduction of Nondividing Cells by a Lentiviral VectorScience, 1996
- Analysis oftrans-Dominant Mutants of the HIV Type 1 Rev Protein for Their Ability to Inhibit Rev Function, HIV Type 1 Replication, and Their Use as Anti-HIV Gene TherapeuticsAIDS Research and Human Retroviruses, 1995
- Inhibition of Human Immunodeficiency Virus Type-1 by Retroviral Vectors Expressing Antisense-TARHuman Gene Therapy, 1994
- Transfer of an Anti-HIV-1 Ribozyme Gene into Primary Human LymphocytesHuman Gene Therapy, 1994
- HIV-1 Reverse Transcription A Termination Step at the Center of the GenomeJournal of Molecular Biology, 1994
- Sequence of the promoter region of the gene for human X-linked 3-phosphoglycerate kinaseGene, 1984