ArticleNucleic acids research2010
Deriving four functional anti-HIV siRNAs from a single Pol III-generated transcript comprising two adjacent long hairpin RNA precursors.
Article in Nucleic acids research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 37 citations in OpenAlex.
- RNA Interference Therapies for an HIV-1 Functional Cure.Viruses · 2017Review
- TALEN/CRISPR-mediated engineering of a promoterless anti-viral RNAi hairpin into an endogenous miRNA locus.Nucleic acids research · 2017Article
- Efficacy Analysis of Combinatorial siRNAs against HIV Derived from One Double Hairpin RNA Precursor.Frontiers in microbiology · 2017Article
- Recent advances in RNAi-based strategies for therapy and prevention of HIV-1/AIDS.Advanced drug delivery reviews · 2016Review
- Design of Effective Primary MicroRNA Mimics With Different Basal Stem Conformations.Molecular therapy. Nucleic acids · 2016Article
- Bone Marrow Gene Therapy for HIV/AIDS.Viruses · 2015Review
- Optimized lentiviral vectors for HIV gene therapy: multiplexed expression of small RNAs and inclusion of MGMT(P140K) drug resistance gene.Molecular therapy : the journal of the American Society of Gene Therapy · 2014Article
- Robust RNAi enhancement via human Argonaute-2 overexpression from plasmids, viral vectors and cell lines.Nucleic acids research · 2013Article
- Creating genetic resistance to HIV.Current opinion in immunology · 2012Review
- Silencing of Parkinson's disease-associated genes with artificial mirtron mimics of miR-1224.Nucleic acids research · 2012Article
- Antiviral RNAi: translating science towards therapeutic success.Pharmaceutical research · 2011Review
- A comparison of multiple shRNA expression methods for combinatorial RNAi.Genetic vaccines and therapy · 2011Article
- RNAi and small interfering RNAs in human disease therapeutic applications.Trends in biotechnology · 2010Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Several different approaches exist to generate expressed RNA interference (RNAi) precursors for multiple target inhibition, a strategy referred to as combinatorial (co)RNAi. One such approach makes use of RNA Pol III-expressed long hairpin RNAs (lhRNAs), which are processed by Dicer to generate multiple unique short interfering siRNA effectors. However, because of inefficient intracellular Dicer processing, lhRNA duplexes have been limited to generating two independent effective siRNA species. In this study, we describe a novel strategy whereby four separate anti-HIV siRNAs were generated from a single RNA Pol III-expressed transcript. Two optimized lhRNAs, each comprising two active anti-HIV siRNAs, were placed in tandem to form a double long hairpin (dlhRNA) expression cassette, which encodes four unique and effective siRNA sequences. Processing of the 3' position lhRNA was more variable but effective multiple processing was possible by manipulating the order of the siRNA-encoding sequences. Importantly, unlike shRNAs, Pol III-expressed dlhRNAs did not compete with endogenous and exogenous microRNAs to disrupt the RNAi pathway. The versatility of expressed lhRNAs is greatly expanded and we provide a mechanism for generating transcripts with modular lhRNAs motifs that contribute to improved coRNAi.
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