ArticleNucleic acids research2016
Periodic-shRNA molecules are capable of gene silencing, cytotoxicity and innate immune activation in cancer cells.
Article in Nucleic acids research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 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.
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Who cites it
7 citing papers in PubMed, 11 citations in OpenAlex.
- Engineering polymeric RNA scaffolds as programmable combinatorial innate immune agonists.Nucleic acids research · 2026Article
- Layer-by-Layer Nanoparticles of Tamoxifen and Resveratrol for Dual Drug Delivery System and Potential Triple-Negative Breast Cancer Treatment.Pharmaceutics · 2021Article
- SSD - a free software for designing multimeric mono-, bi- and trivalent shRNAs.Genetics and molecular biology · 2020Article
- Rationally Designed Polycationic Carriers for Potent Polymeric siRNA-Mediated Gene Silencing.ACS nano · 2018Article
- Engineering nanolayered particles for modular drug delivery.Journal of controlled release : official journal of the Controlled Release Society · 2016Review
- The Antitumor Effect of Metformin Is Mediated by miR-26a in Breast Cancer.International journal of molecular sciences · 2016Article
- Engineering Periodic shRNA for Enhanced Silencing Efficacy.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Large dsRNA molecules can cause potent cytotoxic and immunostimulatory effects through the activation of pattern recognition receptors; however, synthetic versions of these molecules are mostly limited to simple sequences like poly-I:C and poly-A:U. Here we show that large RNA molecules generated by rolling circle transcription fold into periodic-shRNA (p-shRNA) structures and cause potent cytotoxicity and gene silencing when delivered to cancer cells. We determined structural requirements for the dumbbell templates used to synthesize p-shRNA, and showed that these molecules likely adopt a co-transcriptionally folded structure. The cytotoxicity of p-shRNA was robustly observed across four different cancer cell lines using two different delivery systems. Despite having a considerably different folded structure than conventional dsRNA, the cytotoxicity of p-shRNA was either equal to or substantially greater than that of poly-I:C depending on the delivery vehicle. Furthermore, p-shRNA caused greater NF-κB activation in SKOV3 cells compared to poly-I:C, indicating that it is a powerful activator of innate immunity. The tuneable sequence and combined gene silencing, immunostimulatory and cytotoxic capacity of p-shRNA make it an attractive platform for cancer immunotherapy.
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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.