ArticleMolecular therapy : the journal of the American Society of Gene Therapy2012
Robust suppression of HIV replication by intracellularly expressed reverse transcriptase aptamers is independent of ribozyme processing.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 35 citations in OpenAlex.
- Selection and identification of an RNA aptamer that specifically binds the HIV-1 capsid lattice and inhibits viral replication.Nucleic acids research · 2022Article
- Aptamers in Virology-A Consolidated Review of the Most Recent Advancements in Diagnosis and Therapy.Pharmaceutics · 2021Review
- Aptamers for Anti-Viral Therapeutics and Diagnostics.International journal of molecular sciences · 2021Review
- Selection and Characterization of ssDNA Aptamers Targeting Largemouth Bass Virus Infected Cells With Antiviral Activities.Frontiers in microbiology · 2021Article
- Extended Interactions between HIV-1 Viral RNA and tRNAInternational journal of molecular sciences · 2020Article
- 2'-fluoro-modified pyrimidines enhance affinity of RNA oligonucleotides to HIV-1 reverse transcriptase.RNA (New York, N.Y.) · 2020Article
- Binding interface and impact on protease cleavage for an RNA aptamer to HIV-1 reverse transcriptase.Nucleic acids research · 2020Article
- Review
- Activation of Innate Immune Responses by a CpG Oligonucleotide Sequence Composed Entirely of Threose Nucleic Acid.Nucleic acid therapeutics · 2019Article
- Poly-Target Selection Identifies Broad-Spectrum RNA Aptamers.Molecular therapy. Nucleic acids · 2018Article
- Incorporation of aptamers in the terminal loop of shRNAs yields an effective and novel combinatorial targeting strategy.Nucleic acids research · 2018Article
- RNA-protein interactions govern antiviral specificity and encapsidation of broad spectrum anti-HIV reverse transcriptase aptamers.Nucleic acids research · 2017Article
- Aptamers against pathogenic microorganisms.Critical reviews in microbiology · 2016Review
- Selective aptamer-based control of intraneuronal signaling.Angewandte Chemie (International ed. in English) · 2015Article
- High-affinity RNA Aptamers Against the HIV-1 Protease Inhibit Both In Vitro Protease Activity and Late Events of Viral Replication.Molecular therapy. Nucleic acids · 2015Article
- Efficient HIV-1 inhibition by a 16 nt-long RNA aptamer designed by combining in vitro selection and in silico optimisation strategies.Scientific reports · 2014Article
- Aptamer-based therapeutics: new approaches to combat human viral diseases.Pharmaceuticals (Basel, Switzerland) · 2013Article
- Potent Inhibition of HIV-1 Reverse Transcriptase and Replication by Nonpseudoknot, "UCAA-motif" RNA Aptamers.Molecular therapy. Nucleic acids · 2013Article
- High-throughput sequence analysis reveals structural diversity and improved potency among RNA inhibitors of HIV reverse transcriptase.Nucleic acids research · 2013Article
- Aptamers: novel molecules as diagnostic markers in bacterial and viral infections?BioMed research international · 2013Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
RNA aptamers that bind human immunodeficiency virus 1 (HIV-1) reverse transcriptase (RT) also inhibit viral replication, making them attractive as therapeutic candidates and potential tools for dissecting viral pathogenesis. However, it is not well understood how aptamer-expression context and cellular RNA pathways govern aptamer accumulation and net antiviral bioactivity. Using a previously-described expression cassette in which aptamers were flanked by two "minimal core" hammerhead ribozymes, we observed only weak suppression of pseudotyped HIV. To evaluate the importance of the minimal ribozymes, we replaced them with extended, tertiary-stabilized hammerhead ribozymes with enhanced self-cleavage activity, in addition to noncleaving ribozymes with active site mutations. Both the active and inactive versions of the extended hammerhead ribozymes increased inhibition of pseudotyped virus, indicating that processing is not necessary for bioactivity. Clonal stable cell lines expressing aptamers from these modified constructs strongly suppressed infectious virus, and were more effective than minimal ribozymes at high viral multiplicity of infection (MOI). Tertiary stabilization greatly increased aptamer accumulation in viral and subcellular compartments, again regardless of self-cleavage capability. We therefore propose that the increased accumulation is responsible for increased suppression, that the bioactive form of the aptamer is one of the uncleaved or partially cleaved transcripts, and that tertiary stabilization increases transcript stability by reducing exonuclease degradation.
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