ArticleMolecular therapy : the journal of the American Society of Gene Therapy2015
Multiplexing seven miRNA-Based shRNAs to suppress HIV replication.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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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
30 citing papers in PubMed, 42 citations in OpenAlex.
- Article
- Clinical Proof-of-Concept of a Non-Gene Editing Technology Using miRNA-Based shRNA to Engineer Allogeneic CAR T-Cells.International journal of molecular sciences · 2025Article
- Transmucosal Delivery of miR-30c-5p by Chitosan Nanoparticles for Oral Squamous Cell Carcinoma.International journal of nanomedicine · 2025Article
- Allogeneic CART progress: platforms, current progress and limitations.Frontiers in immunology · 2025Review
- In pursuit of an HIV cure: from stem cell transplants to gene therapies.Frontiers in genome editing · 2025Review
- LinQURE: A novel AAV gene silencing platform that supports multi-transcript targeting for complex disorders.Molecular therapy. Nucleic acids · 2024Article
- Review
- Engineering strategies to safely drive CAR T-cells into the future.Frontiers in immunology · 2024Review
- Efficient shRNA-based knockdown of multiple target genes for cell therapy using a chimeric miRNA cluster platform.Molecular therapy. Nucleic acids · 2023Article
- Basic Principles of RNA Interference: Nucleic Acid Types and In Vitro Intracellular Delivery Methods.Micromachines · 2023Review
- Review
- IRF4 downregulation improves sensitivity and endurance of CAR T cell functional capacities.Frontiers in immunology · 2023Article
- Multiplexed shRNA-miRs as a candidate for anti HIV-1 therapy: strategies, challenges, and future potential.Journal, genetic engineering & biotechnology · 2022Review
- miRNA Pathway Alteration in Response to Non-Coding RNA Delivery in Viral Vector-Based Gene Therapy.International journal of molecular sciences · 2022Review
- Endogenous spacing enables co-processing of microRNAs and efficient combinatorial RNAi.Cell reports methods · 2022Article
- Editing out HIV: application of gene editing technology to achieve functional cure.Retrovirology · 2021Review
- Article
- Viral Vectors Applied for RNAi-Based Antiviral Therapy.Viruses · 2020Review
- CRISPR therapy towards an HIV cure.Briefings in functional genomics · 2020Article
- Reduce and Control: A Combinatorial Strategy for Achieving Sustained HIV Remissions in the Absence of Antiretroviral Therapy.Viruses · 2020Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Multiplexed miRNA-based shRNAs (shRNA-miRs) could have wide potential to simultaneously suppress multiple genes. Here, we describe a simple strategy to express a large number of shRNA-miRs using minimal flanking sequences from multiple endogenous miRNAs. We found that a sequence of 30 nucleotides flanking the miRNA duplex was sufficient for efficient processing of shRNA-miRs. We inserted multiple shRNAs in tandem, each containing minimal flanking sequence from a different miRNA. Deep sequencing of transfected cells showed accurate processing of individual shRNA-miRs and that their expression did not decrease with the distance from the promoter. Moreover, each shRNA was as functionally competent as its singly expressed counterpart. We used this system to express one shRNA-miR targeting CCR5 and six shRNA-miRs targeting the HIV-1 genome. The lentiviral construct was pseudotyped with HIV-1 envelope to allow transduction of both resting and activated primary CD4 T cells. Unlike one shRNA-miR, the seven shRNA-miR transduced T cells nearly abrogated HIV-1 infection in vitro. Additionally, when PBMCs from HIV-1 seropositive individuals were transduced and transplanted into NOD/SCID/IL-2R γc(-/-) mice (Hu-PBL model) efficient suppression of endogenous HIV-1 replication with restoration of CD4 T cell counts was observed. Thus, our multiplexed shRNA appears to provide a promising gene therapeutic approach for HIV-1 infection.
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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.