Evidence map›Paper›PMID 34980913›Full record

ArticleNature biotechnology2022

CLUSTER guide RNAs enable precise and efficient RNA editing with endogenous ADAR enzymes in vivo.

Philipp Reautschnig, Nicolai Wahn, Jacqueline Wettengel, Annika E Schulz, Ngadhnjim Latifi, Paul Vogel, Tae-Won Kang, Laura S Pfeiffer, Christine Zarges, Ulrike Naumann and 3 more

Abstract read
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In one paragraph

Article in Nature biotechnology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.

0numbers the graph read from it
0cells of the map it votes in
77citing papers in PubMed
8.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

77 citing papers in PubMed, 104 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Evolution of Engineered ADAR-Based RNA Editing Systems.International journal of molecular sciences · 2026
    Review
  10. Article
  11. Article
  12. A Translational Roadmap for Neurological Nonsense Mutation Disorders.International journal of molecular sciences · 2026
    Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. An ADAR2-mimic base editor for efficient C-to-U RNA editing in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  20. Article

17 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 4 institutions in 2 countries.

Philipp ReautschnigInterfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany.
Nicolai Wahn, Tübingen, Germany.
Jacqueline WettengelInterfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany.
Annika E SchulzInterfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany.
Ngadhnjim LatifiInterfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany.
Paul VogelDepartment of Genetics, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-8384-0712
Tae-Won KangDepartment of Medical Oncology and Pneumology (Internal Medicine VIII), University Hospital Tübingen, Tübingen, Germany.
Laura S PfeifferInterfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany.ORCID http://orcid.org/0000-0002-2487-4138
Christine ZargesInterfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany.
Ulrike NaumannHertie Institute for Clinical Brain Research, Center of Neurology, University Hospital Tübingen, University of Tübingen, Tübingen, Germany.
Lars ZenderDepartment of Medical Oncology and Pneumology (Internal Medicine VIII), University Hospital Tübingen, Tübingen, Germany.
Jin Billy LiDepartment of Genetics, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-0713-1399
Thorsten StafforstInterfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany. thorsten.stafforst@uni-tuebingen.de.ORCID http://orcid.org/0000-0001-9359-3439
University of Tübingen · DEGerman Cancer Research Center · DEStanford University · USHertie Institute for Clinical Brain Research · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

RNA base editing represents a promising alternative to genome editing. Recent approaches harness the endogenous RNA-editing enzyme adenosine deaminase acting on RNA (ADAR) to circumvent problems caused by ectopic expression of engineered editing enzymes, but suffer from sequence restriction, lack of efficiency and bystander editing. Here we present in silico-optimized CLUSTER guide RNAs that bind their target messenger RNAs in a multivalent fashion, achieve editing with high precision and efficiency and enable targeting of sequences that were not accessible using previous gRNA designs. CLUSTER gRNAs can be genetically encoded and delivered using viruses, and are active in a wide range of cell lines. In cell culture, CLUSTER gRNAs achieve on-target editing of endogenous transcripts with yields of up to 45% without bystander editing. In vivo, CLUSTER gRNAs delivered to mouse liver by hydrodynamic tail vein injection edited reporter constructs at rates of up to 10%. The CLUSTER approach opens avenues for drug development in the field of RNA base editing.

Indexed as

RNA EditingAnimalsBase SequenceMiceRNARNA, Guide, CRISPR-Cas SystemsRNA, MessengerRNARNA, Guide, CRISPR-Cas SystemsRNA, Messenger

Identifiers

PMID34980913
OpenAlexW4205602428

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.