Researchers have unveiled a new RNA editing platform that coaxes a cell’s own editing enzyme into correcting RNA transcripts with efficiencies approaching 100 percent in cultured cells and 84 percent in living mice. The system, called MARRS, short for multivalent ADAR1-recruiting RNA editing system, is described in a study published in Nature Methods on 28 October 2026.
Adenosine-to-inosine RNA editing has long been viewed as a promising therapeutic strategy because it can correct mutations at the transcript level without inducing permanent changes to the genome. Yet existing systems have struggled with limited editing efficiency, a constraint that has hindered practical applications.
MARRS tackles this bottleneck by exploiting engineered multivalent RNA aptamers to recruit endogenous ADAR1 enzymes. The team designed aptamers that target the Zα domain of ADAR1 p150.
Two design choices proved decisive. First, the researchers optimized the aptamers themselves for stronger and more reliable engagement of ADAR1 p150.
Multivalency added a further boost. The researchers engineered tandem arrays of aptamers and embedded them in a circular RNA scaffold, presenting multiple recruitment modules for the enzyme. According to the study, this engineering strategy enabled near-complete adenosine-to-inosine editing of RNA targets, with efficiencies reaching up to 100 percent in vitro and 84 percent in vivo in mouse models.
The platform also demonstrated remarkable versatility, functioning across a range of transcript targets. Equally important, the authors report that MARRS maintains high specificity, with minimal off-target effects, a critical requirement for any editing technology intended for research or therapeutic use.
Because MARRS operates without the need for exogenous enzymes, the researchers describe it as a safe, efficient and programmable platform.
The work, with Han Zhu as first author and Shu-Lin Liu among the authors, appears in Nature Methods. The published figures include evaluations of aptamer reprogramming, guide RNA truncation and circularization, tandem aptamer engineering, and in vivo editing efficiency, laying out the stepwise development of the system from design to animal testing.
If the reported efficiencies and specificity hold up in broader testing, MARRS could expand the toolkit for transcript-level correction of disease-associated mutations, offering a programmable alternative that leverages the cell’s own editing machinery rather than replacing it.
Subject of Research: Development of an RNA editing platform that recruits endogenous ADAR1 using multivalent circular RNA aptamers
Article Title: Aptamer-mediated multivalent endogenous ADAR1 recruitment for highly efficient RNA editing
Article References: Zhu, H., Zhou, Y., Huang, R., Wang, Y.-F., Hu, Y., Wang, L., Jin, J.-H., Ye, Q., Liu, X., Wang, Z.-G., Xie, H.-Y., Li, J. B., Pang, D.-W., & Liu, S.-L. (2026). Aptamer-mediated multivalent endogenous ADAR1 recruitment for highly efficient RNA editing. Nature Methods. https://doi.org/10.1038/s41592-026-03284-7
Image Credits: AI Generated
DOI: 10.1038/s41592-026-03284-7
Keywords: RNA editing, ADAR1, MARRS, circular RNA, aptamers, adenosine-to-inosine, Nature Methods, gene therapy, transcript editing, off-target effects, Aptamer-mediated, multivalent
News Source: Gregory Coleman. (October 28, 2026). Circular RNA aptamers recruit natural ADAR1 to edit RNA with near-perfect efficiency. Scienmag.
