ArticleGene therapy2009
Evaluation of safety and efficacy of RNAi against HIV-1 in the human immune system (Rag-2(-/-)gammac(-/-)) mouse model.
Article in Gene therapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 77 citations in OpenAlex.
- AMF siRNA treatment of keloid through inhibition signaling pathway of RhoA/ROCK1.Genes & diseases · 2019Article
- Gene Therapy Approaches to Functional Cure and Protection of Hematopoietic Potential in HIV Infection.Pharmaceutics · 2019Review
- The therapeutic landscape of HIV-1 via genome editing.AIDS research and therapy · 2017Review
- Efficient inhibition of human immunodeficiency virus replication using novel modified microRNA-30a targeting 3'-untranslated region transcripts.Experimental and therapeutic medicine · 2016Article
- 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
- The impact of HIV-1 genetic diversity on the efficacy of a combinatorial RNAi-based gene therapy.Gene therapy · 2015Article
- RNA interference approaches for treatment of HIV-1 infection.Genome medicine · 2015Article
- The impact of unprotected T cells in RNAi-based gene therapy for HIV-AIDS.Molecular therapy : the journal of the American Society of Gene Therapy · 2014Article
- Silencing of HIV-1 gag gene from epidemic strains among men who have sex with men (MSM) in Tianjin, China by a broad-spectrum short hairpin RNA.Virusdisease · 2014Article
- Lipid nanoparticles as carriers for RNAi against viral infections: current status and future perspectives.BioMed research international · 2014Review
- Review
- Promoter Targeting shRNA Suppresses HIV-1 Infection In vivo Through Transcriptional Gene Silencing.Molecular therapy. Nucleic acids · 2013Article
- Preclinical in vivo evaluation of the safety of a multi-shRNA-based gene therapy against HIV-1.Molecular therapy. Nucleic acids · 2013Article
- New generation humanized mice for virus research: comparative aspects and future prospects.Virology · 2013Review
- Highly significant antiviral activity of HIV-1 LTR-specific tre-recombinase in humanized mice.PLoS pathogens · 2013Article
- CD25 preselective anti-HIV vectors for improved HIV gene therapy.Human gene therapy methods · 2012Article
- A doxycycline-dependent human immunodeficiency virus type 1 replicates in vivo without inducing CD4+ T-cell depletion.The Journal of general virology · 2012Article
- Efficient inhibition of HIV-1 replication by an artificial polycistronic miRNA construct.Virology journal · 2012Article
- HIV-1 Escape From RNAi Antivirals: Yet Another Houdini Action?Molecular therapy. Nucleic acids · 2012Article
- Selection of RNAi-based inhibitors for anti-HIV gene therapy.World journal of virology · 2012Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
RNA interference (RNAi) gene therapy against HIV-1 by stable expression of antiviral short hairpin RNAs (shRNAs) can potently inhibit viral replication in T cells. Recently, a mouse model with a human immune system (HIS) was developed that can be productively infected with HIV-1. In this in vivo model, in which Rag-2(-/-)gamma(c)(-/-) mice are engrafted with human CD34(+)CD38(-) hematopoietic precursor cells, we evaluated an anti-HIV RNAi gene therapy. Human hematopoietic stem cells were transduced with a lentiviral vector expressing an shRNA against the HIV-1 nef gene (shNef) or the control vector. We observed normal development of the different cell subsets of the immune system. However, although initial transduction efficiencies were similar for both vectors, a reduced percentage of transduced human immune cells was observed for the shNef vector after establishment of the HIS in vivo. Further studies are required to fully evaluate the safety implications. When we infected the mature human CD4(+) T cells from the HIS mouse ex vivo with HIV-1, potent inhibition of viral replication was scored in shNef-expressing cells, confirming efficacy. When challenged with an shNef-resistant HIV-1 variant, equal replication was scored in control and shNef-expressing cells, confirming sequence-specificity of the RNAi therapy. We thus demonstrated that an antiviral RNAi-based gene therapy on blood stem cells leads to HIV-1-resistant T cells in vivo, an important proof of concept in the clinical development of RNAi against HIV-1.
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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.