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Identification of Circular RNAs using RNA Sequencing
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Programmable RNA editing by recruiting endogenous ADAR using engineered RNAs.

Liang Qu1,2, Zongyi Yi1,3, Shiyou Zhu1

  • 1Biomedical Pioneering Innovation Center, Beijing Advanced Innovation Center for Genomics, Peking-Tsinghua Center for Life Sciences, Peking University Genome Editing Research Center, State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China.

Nature Biotechnology
|July 17, 2019

View abstract on PubMed

Summary
This summary is machine-generated.

We developed LEAPER (leveraging endogenous ADAR for programmable editing of RNA), a new RNA editing tool using engineered RNAs to recruit native enzymes. This precise and efficient method shows broad applicability for therapy and research.

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Area of Science:

  • Molecular Biology
  • Genetic Engineering
  • RNA Therapeutics

Background:

  • Current RNA editing tools face challenges like immunogenicity and delivery barriers.
  • Exogenous proteins or modified guide RNAs can cause unwanted effects.

Purpose of the Study:

  • To introduce a novel, efficient, and specific RNA editing system.
  • To overcome limitations of existing RNA editing technologies.

Main Methods:

  • Developed LEAPER (leveraging endogenous ADAR for programmable editing of RNA) using engineered ADAR-recruiting RNAs (arRNAs).
  • Delivered arRNAs via plasmids, viral vectors, or synthetic oligonucleotides.
  • Tested editing efficiency, specificity, and cellular activity in various cell types.

Main Results:

  • Achieved up to 80% RNA editing efficiency with LEAPER.
  • Demonstrated high specificity with rare off-target edits.
  • Showed LEAPER's activity across diverse cell types, including primary human cells.
  • Restored enzyme activity in Hurler syndrome fibroblasts without immune response.

Conclusions:

  • LEAPER offers a precise and efficient single-molecule system for RNA editing.
  • The approach has broad applicability for therapeutic interventions and basic research.
  • LEAPER minimizes immunogenicity and delivery challenges associated with other methods.