Evidence map›Paper›PMID 32978399›Full record

ArticleNature communications2020

Engineering domain-inlaid SaCas9 adenine base editors with reduced RNA off-targets and increased on-target DNA editing.

Minh Thuan Nguyen Tran, Mohd Khairul Nizam Mohd Khalid, Qi Wang, Jacqueline K R Walker, Grace E Lidgerwood, Kimberley L Dilworth, Leszek Lisowski, Alice Pébay, Alex W Hewitt

Abstract read
In one paragraph

Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
–field-weighted citation impact
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

47 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Efforts to Downsize Base Editors for Clinical Applications.International journal of molecular sciences · 2025
    Review
  11. Article
  12. Article
  13. A Manual for Genome and Transcriptome Engineering.IEEE reviews in biomedical engineering · 2025
    Review
  14. Rational Design of Enhanced Nme2Cas9 and Nme2bioRxiv : the preprint server for biology · 2024
    Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
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

9 authors.

Minh Thuan Nguyen TranMenzies Institute for Medical Research, School of Medicine, University of Tasmania, Tasmania, Australia. pherominh1@gmail.com.ORCID http://orcid.org/0000-0002-9554-6449
Mohd Khairul Nizam Mohd KhalidMenzies Institute for Medical Research, School of Medicine, University of Tasmania, Tasmania, Australia.
Qi WangMenzies Institute for Medical Research, School of Medicine, University of Tasmania, Tasmania, Australia.
Jacqueline K R WalkerMenzies Institute for Medical Research, School of Medicine, University of Tasmania, Tasmania, Australia.
Grace E LidgerwoodDepartment of Surgery, The University of Melbourne, Victoria, Australia.
Kimberley L DilworthTranslational Vectorology Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, Australia.
Leszek LisowskiTranslational Vectorology Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, Australia.ORCID http://orcid.org/0000-0002-4772-8651
Alice PébayDepartment of Surgery, The University of Melbourne, Victoria, Australia.ORCID http://orcid.org/0000-0002-7408-9453
Alex W HewittMenzies Institute for Medical Research, School of Medicine, University of Tasmania, Tasmania, Australia.ORCID http://orcid.org/0000-0002-5123-5999

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Precision genome engineering has dramatically advanced with the development of CRISPR/Cas base editing systems that include cytosine base editors and adenine base editors (ABEs). Herein, we compare the editing profile of circularly permuted and domain-inlaid Cas9 base editors, and find that on-target editing is largely maintained following their intradomain insertion, but that structural permutation of the ABE can affect differing RNA off-target events. With this insight, structure-guided design was used to engineer an SaCas9 ABE variant (microABE I744) that has dramatically improved on-target editing efficiency and a reduced RNA-off target footprint compared to current N-terminal linked SaCas9 ABE variants. This represents one of the smallest AAV-deliverable Cas9-ABEs available, which has been optimized for robust on-target activity and RNA-fidelity based upon its stereochemistry.

Indexed as

CRISPR-Cas SystemsAdenineCRISPR-Associated Protein 9CytosineDNAExomeGene EditingGenetic EngineeringGenomeHEK293 CellsHumansRNARNA EditingAdenineCRISPR-Associated Protein 9CytosineDNARNA

Identifiers

PMID32978399
PMCPMC7519688

What OpenQuestion holds

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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.