ArticleAIDS research and therapy2005
HIV-1 resistance conferred by siRNA cosuppression of CXCR4 and CCR5 coreceptors by a bispecific lentiviral vector.
Article in AIDS research and therapy, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 94 citations in OpenAlex.
- The Association betweenViruses · 2023Pooled it
- Defensins: defenders of human reproductive health.Human reproduction update · 2023Review
- Lentivirus-Mediated VEGF Knockdown Suppresses Gastric Cancer Cell Proliferation and Tumor Growth in vitro and in vivo.OncoTargets and therapy · 2020Article
- Advancement of the Emerging Field of RNA Nanotechnology.ACS nano · 2017Review
- Review
- Development of Lentiviral Vectors Simultaneously Expressing Multiple siRNAs Against CCR5, vif and tat/rev Genes for an HIV-1 Gene Therapy Approach.Molecular therapy. Nucleic acids · 2016Article
- Cell-based gene therapy against HIV.Gene therapy · 2015Review
- Engineering T Cells to Functionally Cure HIV-1 Infection.Molecular therapy : the journal of the American Society of Gene Therapy · 2015Review
- A novel approach to block HIV-1 coreceptor CXCR4 in non-toxic manner.Molecular biotechnology · 2014Article
- Δ(9)-Tetrahydrocannabinol treatment during human monocyte differentiation reduces macrophage susceptibility to HIV-1 infection.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2014Article
- Gene therapy targeting HIV entry.Viruses · 2014Review
- Preclinical safety and efficacy of an anti-HIV-1 lentiviral vector containing a short hairpin RNA to CCR5 and the C46 fusion inhibitor.Molecular therapy. Methods & clinical development · 2014Article
- Novel cell and gene therapies for HIV.Cold Spring Harbor perspectives in medicine · 2012Review
- Zinc-finger nuclease editing of human cxcr4 promotes HIV-1 CD4(+) T cell resistance and enrichment.Molecular therapy : the journal of the American Society of Gene Therapy · 2012Article
- Inhibition of HIV-1 infection by human α-defensin-5, a natural antimicrobial peptide expressed in the genital and intestinal mucosae.PloS one · 2012Article
- Restriction of the felid lentiviruses by a synthetic feline TRIM5-CypA fusion.Veterinary immunology and immunopathology · 2011Review
- A comparison of multiple shRNA expression methods for combinatorial RNAi.Genetic vaccines and therapy · 2011Article
- Stem cell-based anti-HIV gene therapy.Virology · 2011Review
- Multiple shRNA combinations for near-complete coverage of all HIV-1 strains.AIDS research and therapy · 2011Article
- The use of cell-delivered gene therapy for the treatment of HIV/AIDS.Immunologic research · 2010Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
backgroundRNA interference (RNAi) mediated by small interfering RNAs (siRNAs) has proved to be a highly effective gene silencing mechanism with great potential for HIV/AIDS gene therapy. Previous work with siRNAs against cellular coreceptors CXCR4 and CCR5 had shown that down regulation of these surface molecules could prevent HIV-1 entry and confer viral resistance. Since monospecific siRNAs targeting individual coreceptors are inadequate in protecting against both T cell tropic (X4) and monocyte tropic (R5) viral strains simultaneously, bispecific constructs with dual specificity are required. For effective long range therapy, the bispecific constructs need to be stably transduced into HIV-1 target cells via integrating viral vectors.
resultsTo achieve this goal, lentiviral vectors incorporating both CXCR4 and CCR5 siRNAs of short hairpin design were constructed. The CXCR4 siRNA was driven by a U6 promoter whereas the CCR5 siRNA was driven by an H1 promoter. A CMV promoter driven EGFP reporter gene is also incorporated in the bispecific construct. High efficiency transduction into coreceptor expressing Magi and Ghost cell lines with a concomitant down regulation of respective coreceptors was achieved with lentiviral vectors. When the siRNA expressing transduced cells were challenged with X4 and R5 tropic HIV-1, they demonstrated marked viral resistance. HIV-1 resistance was also observed in bispecific lentiviral vector transduced primary PBMCs.
conclusionsBoth CXCR4 and CCR5 coreceptors could be simultaneously targeted for down regulation by a single combinatorial lentiviral vector incorporating respective anti-coreceptor siRNAs. Stable down regulation of both the coreceptors protects cells against infection by both X4 and R5 tropic HIV-1. Stable down regulation of cellular molecules that aid in HIV-1 infection will be an effective strategy for long range HIV gene therapy.
Identifiers
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Registered trials
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.