ArticleMolecular therapy. Nucleic acids2022
Programmable siRNA pro-drugs that activate RNAi activity in response to specific cellular RNA biomarkers.
Article in Molecular therapy. Nucleic acids, 2022. 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, 18 citations in OpenAlex.
- Tripled-Stranded Antisense Oligonucleotide for Biomarker-Activated Suppression of Essential Genes.Chembiochem : a European journal of chemical biology · 2026Article
- Mammalian therapeutic riboswitches: Engineering and custom ligands.Molecular therapy. Nucleic acids · 2026Review
- Advancements in RNA-based therapies from bench to bedside.npj drug discovery · 2026Review
- Switching off hypertrophy: Conditional siRNA as a precision tool for heart failure therapy.Molecular therapy. Nucleic acids · 2025Article
- Breakthroughs in the nanoparticle-mediated delivery of siRNA for breast cancer treatment.Nanomedicine (London, England) · 2025Review
- Development of conditional-siRNA programmable riboswitch for targeting adverse cardiac remodeling.Molecular therapy. Nucleic acids · 2025Article
- Unlocking the dark matter: noncoding RNAs and RNA modifications in cardiac aging.American journal of physiology. Heart and circulatory physiology · 2024Review
- RNA-based medicine: from molecular mechanisms to therapy.The EMBO journal · 2023Review
- Progressing nanotechnology to improve targeted cancer treatment: overcoming hurdles in its clinical implementation.Molecular cancer · 2023Review
- An inhibitory circuit-based enhancer of DYRK1A function reverses Dyrk1a-associated impairment in social recognition.Neuron · 2023Article
- Triggering RNA Interference by Photoreduction under Red Light Irradiation.Molecules (Basel, Switzerland) · 2023Article
- Modular, programmable RNA sensing using ADAR editing in living cells.Nature biotechnology · 2023Article
- Biomaterials for recruiting and activating endogenous stem cells in situ tissue regeneration.Acta biomaterialia · 2022Review
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
Since Paul Ehrlich's introduction of the "magic bullet" concept in 1908, drug developers have been seeking new ways to target drug activity to diseased cells while limiting effects on normal tissues. In recent years, it has been proposed that coupling riboswitches capable of detecting RNA biomarkers to small interfering RNAs (siRNAs) to create siRNA pro-drugs could selectively activate RNA interference (RNAi) activity in specific cells. However, this concept has not been achieved previously. We report here that we have accomplished this goal, validating a simple and programmable new design that functions reliably in mammalian cells. We show that these conditionally activated siRNAs (Cond-siRNAs) can switch RNAi activity against different targets between clearly distinguished OFF and ON states in response to different cellular RNA biomarkers. Notably, in a rat cardiomyocyte cell line (H9C2), one version of our construct demonstrated biologically meaningful inhibition of a heart-disease-related target gene protein phosphatase 3 catalytic subunit alpha (PPP3CA) in response to increased expression of the pathological marker atrial natriuretic peptide (NPPA) messenger RNA (mRNA). Our results demonstrate the ability of synthetic riboswitches to regulate gene expression in mammalian cells, opening a new path for development of programmable siRNA pro-drugs.
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Registered trials
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