ArticleMolecular therapy : the journal of the American Society of Gene Therapy2008
Lentiviral vector design for multiple shRNA expression and durable HIV-1 inhibition.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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23 citing papers in PubMed, 240 citations in OpenAlex.
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- A novel treatment approach for retinoblastoma by targeting epithelial growth factor receptor expression with a shRNA lentiviral system.Iranian journal of basic medical sciences · 2017Article
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- The impact of HIV-1 genetic diversity on the efficacy of a combinatorial RNAi-based gene therapy.Gene therapy · 2015Article
- A novel approach to block HIV-1 coreceptor CXCR4 in non-toxic manner.Molecular biotechnology · 2014Article
- Efficient viral delivery system for unnatural amino acid mutagenesis in mammalian cells.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Construction of multiple shRNAs expression vector that inhibits FUT1 gene expression and production of the transgenic SCNT embryos in vitro.Molecular biology reports · 2013Article
- A novel lentivirus for quantitative assessment of gene knockdown in stem cell differentiation.Gene therapy · 2012Review
- Selection of RNAi-based inhibitors for anti-HIV gene therapy.World journal of virology · 2012Review
- Directed HIV-1 evolution of protease inhibitor resistance by second-generation short hairpin RNAs.Antimicrobial agents and chemotherapy · 2012Article
- Current progress in the development of RNAi-based therapeutics for HIV-1.Gene therapy · 2011Review
- Inhibition of cervical cancer cell growth in vitro and in vivo with dual shRNAs.Cancer gene therapy · 2011Article
- Efficient downregulation of multiple mRNA targets with a single shRNA-expressing lentiviral vector.Plasmid · 2010Article
- Toward a durable anti-HIV gene therapy based on RNA interference.Annals of the New York Academy of Sciences · 2009Review
- Non-coding RNAs: Bridging Biology and Therapy.Journal of RNAi and gene silencing : an international journal of RNA and gene targeting research · 2009Article
- Simultaneous knockdown of the expression of two genes using multiple shRNAs and subsequent knock-in of their expression.Nature protocols · 2009Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human immunodeficiency virus type 1 (HIV-1) replication in T cells can be inhibited by RNA interference (RNAi) through short hairpin RNA (shRNA) expression from a lentiviral vector. However, for the development of a durable RNAi-based gene therapy against HIV-1, multiple shRNAs need to be expressed simultaneously in order to avoid viral escape. In this study, we tested a multiple shRNA expression strategy for different shRNAs using repeated promoters in a lentiviral vector. Although highly effective in co-transfection experiments, a markedly reduced activity of each expressed shRNA was observed in transduced cells. We found that this reduced activity was due to recombination of the expression cassette repeat sequences during the transduction of the lentiviral vector, which resulted in deletions of one or multiple cassettes. To avoid recombination, we tested different promoters for multiple shRNA expression. We compared the activity of the human polymerase III promoters U6, H1, and 7SK and the polymerase II U1 promoter. Activities of these promoters were similar, irrespective of which shRNA was expressed. We showed that these four expression cassettes can be combined in a single lentiviral vector without causing recombination. Moreover, whereas HIV-1 could escape from a single shRNA, we now show that HIV-1 escape can be prevented when four shRNAs are simultaneously expressed in a cell.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.