ArticleMolecular therapy : the journal of the American Society of Gene Therapy2013
Durable knockdown and protection from HIV transmission in humanized mice treated with gel-formulated CD4 aptamer-siRNA chimeras.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
38 citing papers in PubMed, 73 citations in OpenAlex.
- Review
- RNAi-based drug design: considerations and future directions.Nature reviews. Drug discovery · 2024Review
- Dynamic RNA synthetic biology: new principles, practices and potential.RNA biology · 2023Review
- Multiplexed shRNA-miRs as a candidate for anti HIV-1 therapy: strategies, challenges, and future potential.Journal, genetic engineering & biotechnology · 2022Review
- Fused deposition modeling three-dimensional printing of flexible polyurethane intravaginal rings with controlled tunable release profiles for multiple active drugs.Drug delivery and translational research · 2022Article
- Discovery and Use of Long dsRNA Mediated RNA Interference to Stimulate Antiviral Protection in Interferon Competent Mammalian Cells.Frontiers in immunology · 2022Article
- Aptamers in Virology-A Consolidated Review of the Most Recent Advancements in Diagnosis and Therapy.Pharmaceutics · 2021Review
- Nucleic Acid-Based Treatments Against COVID-19: Potential Efficacy of Aptamers and siRNAs.Frontiers in microbiology · 2021Review
- Self-Assembled Multivalent Aptamer Nanoparticles with Potential CAR-like Characteristics Could Activate T Cells and Inhibit Melanoma Growth.Molecular therapy oncolytics · 2020Article
- Advances in Humanized Mouse Models to Improve Understanding of HIV-1 Pathogenesis and Immune Responses.Frontiers in immunology · 2020Review
- Review
- Axl-Targeted Delivery of the Oncosuppressor miR-137 in Non-small-Cell Lung Cancer.Molecular therapy. Nucleic acids · 2019Article
- Bispecific therapeutic aptamers for targeted therapy of cancer: a review on cellular perspective.Journal of molecular medicine (Berlin, Germany) · 2018Review
- Aptamers in HIV research diagnosis and therapy.RNA biology · 2018Review
- STAT3 Gene Silencing by Aptamer-siRNA Chimera as Selective Therapeutic for Glioblastoma.Molecular therapy. Nucleic acids · 2018Article
- Aptamers for CD Antigens: From Cell Profiling to Activity Modulation.Molecular therapy. Nucleic acids · 2017Review
- Advancement of the Emerging Field of RNA Nanotechnology.ACS nano · 2017Review
- Human CD64-targeted non-viral siRNA delivery system for blood monocyte gene modulation.Scientific reports · 2017Article
- Aptamers against pathogenic microorganisms.Critical reviews in microbiology · 2016Review
- The delivery of therapeutic oligonucleotides.Nucleic acids research · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
The continued spread of HIV underscores the need to interrupt transmission. One attractive strategy, in the absence of an effective vaccine, is a topical microbicide, but the need for application around the time of sexual intercourse leads to poor patient compliance. Intravaginal (IVAG) application of CD4 aptamer-siRNA chimeras (CD4-AsiCs) targeting the HIV coreceptor CCR5, gag, and vif protected humanized mice from sexual transmission. In non-dividing cells and tissue, RNAi-mediated gene knockdown lasts for several weeks, providing an opportunity for infrequent dosing not temporally linked to sexual intercourse, when compliance is challenging. Here, we investigate the durability of gene knockdown and viral inhibition, protection afforded by CCR5 or HIV gene knockdown on their own, and effectiveness of CD4-AsiCs formulated in a gel in polarized human cervicovaginal explants and in humanized mice. CD4-AsiC-mediated gene knockdown persisted for several weeks. Cell-specific gene knockdown and protection were comparable in a hydroxyethylcellulose gel formulation. CD4-AsiCs against CCR5 or gag/vif performed as well as a cocktail in humanized mice. Transmission was completely blocked by CCR5 CD4-AsiCs applied 2 days before challenge. Significant, but incomplete, protection also occurred when exposure was delayed for 4 or 6 days. CD4-AsiCs targeting gag/vif provided some protection when administered only after exposure. These data suggest that CD4-AsiCs are a promising approach for developing an HIV microbicide.
Indexed as
Identifiers
What OpenQuestion holds
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.