ArticleNature biomedical engineering2026
Engineering drug-responsive replication machinery for precise control of self-amplifying RNA.
Article in Nature biomedical engineering, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
What it found
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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
4 citing papers in PubMed.
- Bioengineering strategies for improving the immunogenicity of mRNA vaccines.Signal transduction and targeted therapy · 2026Review
- Engineering the Future of Precision Medicine: A Comprehensive Guide to RNA Therapeutics.Current issues in molecular biology · 2026Review
- Pharmacological evolution of natural product-based and chemically engineered autophagy-modulating strategies in neurodegenerative diseases: a bibliometric mapping analysis (2006-2025).Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Genetic Medicine Approaches for Tumor Suppressor Loss: Therapeutic Replacement with Self-Amplifying RNA.Pharmaceutical research · 2026Review
Corrections and comments
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Authors and funding
21 authors.
Funding
Abstract
Precise, reversible control of gene expression from self‑amplifying RNA (saRNA) remains difficult, limiting the therapeutic flexibility of this otherwise potent platform. Although alphavirus‑derived saRNAs encode non‑structural proteins that drive RNA replication and offer an intrinsic regulatory point, no existing approach has enabled direct, drug‑dependent control of this machinery for high‑fidelity modulation of expression. Here we engineer saRNA constructs whose replication is activated by the approved small‑molecule drug trimethoprim, using drug‑responsive degradation domains fused to individual non‑structural proteins to regulate self‑amplification. As each replication protein contributes differently to RNA copying, we systematically screened fusion configurations and identified an optimal design combining modified replication proteins with a regulated payload. This construct achieved more than a 10
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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.