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RNA editing is a post-transcriptional modification where a precursor mRNA (pre-mRNA) nucleotide sequence is changed by base insertion, deletion, or modification. The extent of RNA editing varies from a few hundred bases, in mitochondrial DNA of trypanosomes, to a just single base, in nuclear genes of mammals. Even a single base change in the pre-mRNA can convert a codon for one amino acid into the codon for another amino acid or a stop codon. This type of re-coding can significantly affect the...
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Evolution of Engineered ADAR-Based RNA Editing Systems.

Lidia Borkiewicz1

  • 1Department of Biochemistry and Molecular Biology, Medical University of Lublin, Chodzki 1, 20-093 Lublin, Poland.

International Journal of Molecular Sciences
|February 27, 2026
PubMed
Summary

RNA editing, particularly adenosine to inosine (A-to-I) conversion by ADARs, offers a powerful way to modify mRNA. Advances focus on engineering precise ADAR systems for therapeutic applications.

Keywords:
ADARRNA editingRNA-based therapyadenine deamination

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Area of Science:

  • Molecular Biology
  • Genetics
  • Biotechnology

Background:

  • RNA editing diversifies the transcriptome and regulates gene expression.
  • Adenosine deaminases acting on RNA (ADARs) catalyze the common A-to-I RNA editing.
  • ADARs are explored for mRNA rewriting to correct mutations.

Purpose of the Study:

  • To review advances in ADAR-mediated RNA editing technologies.
  • To highlight strategies for enhancing specificity, yield, and targetability.
  • To discuss challenges in delivery and application for research and therapy.

Main Methods:

  • Evolution of ADAR systems from antisense oligonucleotide-guided recruitment to engineered enzymes.
  • Development of systems incorporating additional RNA-binding proteins.
  • Rational design of ADARs for nucleotide conversion and signal amplification.

Main Results:

  • Progress in developing controllable ADAR-based systems for targeted RNA editing.
  • Demonstration of strategies to increase specificity and editing yield.
  • Identification of methods to expand targetable sites and reduce off-target effects.

Conclusions:

  • ADAR-mediated RNA editing shows promise for therapeutic applications.
  • Key challenges include improving specificity, yield, and delivery efficiency.
  • Further optimization is needed for broad cell type applicability and in vivo studies.