ArticleMolecular therapy. Nucleic acids2013
Promoter Targeting shRNA Suppresses HIV-1 Infection In vivo Through Transcriptional Gene Silencing.
Article in Molecular therapy. Nucleic acids, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 61 citations in OpenAlex.
- Beyond Antiretroviral Therapy: Molecular and Immunological Innovations in HIV Treatment.Tropical medicine and infectious disease · 2026Review
- Block-and-Lock Approaches for HIV Cure: Mechanistic Insights, Challenges, and Emerging Role of CPSF6.International journal of molecular sciences · 2026Review
- Breaking into HIV-1's Epigenetic Vault: Cure Strategies to Eliminate the Viral Reservoir.Viruses · 2026Review
- Harnessing antiviral RNAi therapeutics for pandemic viruses: SARS-CoV-2 and HIV.Drug delivery and translational research · 2025Review
- A CRISPR/RfxCas13d-mediated strategy for efficient RNA knockdown in mouse embryonic development.Science China. Life sciences · 2024Article
- Current State of Therapeutics for HTLV-1.Viruses · 2024Review
- MicroRNAs and long non-coding RNAs during transcriptional regulation and latency of HIV and HTLV.Retrovirology · 2024Review
- Advances in HIV Gene Therapy.International journal of molecular sciences · 2024Review
- Insights Into Persistent HIV-1 Infection and Functional Cure: Novel Capabilities and Strategies.Frontiers in microbiology · 2022Review
- HIV-1 viral blips are associated with repeated and increasingly high levels of cell-associated HIV-1 RNA transcriptional activity.AIDS (London, England) · 2021Article
- Aptamer-mediated transcriptional gene silencing ofMolecular therapy. Nucleic acids · 2021Article
- Addressing an HIV cure in LMIC.Retrovirology · 2021Review
- Article
- Block and Lock HIV Cure Strategies to Control the Latent Reservoir.Frontiers in cellular and infection microbiology · 2020Review
- Structure-guided drug design identifies a BRD4-selective small molecule that suppresses HIV.The Journal of clinical investigation · 2019Article
- The current state and future directions of RNAi-based therapeutics.Nature reviews. Drug discovery · 2019Review
- Gene Therapy Approaches to Functional Cure and Protection of Hematopoietic Potential in HIV Infection.Pharmaceutics · 2019Review
- Current Status of Latency Reversing Agents Facing the Heterogeneity of HIV-1 Cellular and Tissue Reservoirs.Frontiers in microbiology · 2019Review
- Stable Transcriptional Repression and Parasitism of HIV-1.Molecular therapy. Nucleic acids · 2018Article
- Generation of HIV-Resistant Macrophages from IPSCs by Using Transcriptional Gene Silencing and Promoter-Targeted RNA.Molecular therapy. Nucleic acids · 2018Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite prolonged and intensive application, combined antiretroviral therapy cannot eradicate human immunodeficiency virus (HIV)-1 because it is harbored as a latent infection, surviving for long periods of time. Alternative approaches are required to overcome the limitations of current therapy. We have been developing a short interfering RNA (siRNA) gene silencing approach. Certain siRNAs targeting promoter regions of genes induce transcriptional gene silencing. We previously reported substantial transcriptional gene silencing of HIV-1 replication by an siRNA targeting the HIV-1 promoter in vitro. In this study, we show that this siRNA, expressed as a short hairpin RNA (shRNA) (shPromA-JRFL) delivered by lentiviral transduction of human peripheral blood mononuclear cells (PBMCs), which are then used to reconstitute NOJ mice, is able to inhibit HIV-1 replication in vivo, whereas a three-base mismatched variant (shPromA-M2) does not. In shPromA-JRFL-treated mice, HIV-1 RNA in serum is significantly reduced, and the ratio of CD4(+)/CD8(+) T cells is significantly elevated. Expression levels of the antisense RNA strand inversely correlates with HIV-1 RNA in serum. The silenced HIV-1 can be reactivated by T-cell activation in ex vivo cultures. HIV-1 suppression is not due to offtarget effects of shPromA-JRFL. These data provide "proof-of principle" that an shRNA targeting the HIV-1 promoter is able to suppress HIV-1 replication in vivo.Molecular Therapy-Nucleic Acids (2013) 2, e137; doi:10.1038/mtna.2013.64; published online 3 December 2013.
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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.