Evidence map›Paper›PMID 38368418›Full record

ArticleNature communications2024

Domain-inlaid Nme2Cas9 adenine base editors with improved activity and targeting scope.

Nathan Bamidele, Han Zhang, Xiaolong Dong, Haoyang Cheng, Nicholas Gaston, Hailey Feinzig, Hanbing Cao, Karen Kelly, Jonathan K Watts, Jun Xie and 2 more

Abstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing 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

16 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Review
  6. Article
  7. Embedded CRISPRi Enhances Gene-Silencing Efficiency in Drosophila.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  8. Article
  9. A compact base editor rescues AATD-associated liver and lung disease in mouse models.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  10. Article
  11. Article
  12. Efforts to Downsize Base Editors for Clinical Applications.International journal of molecular sciences · 2025
    Review
  13. Enhanced Genome Editing Activity with Novel Chimeric ScCas9 Variants in Rice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  14. Rational Design of Enhanced Nme2Cas9 and Nme2bioRxiv : the preprint server for biology · 2024
    Article
  15. Review
  16. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Nathan BamideleRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.ORCID 0000-0001-9051-5531
Han ZhangRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.
Xiaolong DongTessera Therapeutics, Somerville, MA, 02143, USA.
Haoyang ChengRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.
Nicholas GastonRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.ORCID 0000-0002-3862-9002
Hailey FeinzigRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.ORCID 0009-0002-0087-3218
Hanbing CaoRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.
Karen KellyRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.
Jonathan K WattsRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.ORCID 0000-0001-5706-1734
Jun XieHorae Gene Therapy Center, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.ORCID 0000-0001-9565-1567
Guangping GaoHorae Gene Therapy Center, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.ORCID 0000-0003-0097-9012
Erik J SontheimerRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA. erik.sontheimer@umassmed.edu.ORCID 0000-0002-0881-0310

Funding

Advanced Delivery Platforms for Base Editing In VivoR01GM150273 · NIGMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI ERIK J. SONTHEIMER, Wen Xue · 2023 to 2026
$2.4M
Enhancing the success of underrepresented students in the biomedical sciencesR25GM113686 · NIGMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI LAPANE, KATE L, LEWIS, BRIAN C · 2015 to 2019
$1.7M
Engineering Synthetic Guide RNAs and Compact Base Editors for Enhanced In Vivo DeliveryF31GM143879 · NIGMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI BAMIDELE, NATHAN · 2021 to 2022
$67k
NIGMS NIH HHS F31 GM143879NIGMS NIH HHS R01 GM150273NIGMS NIH HHS R25 GM113686
6 · The paper itself

Abstract

Nme2Cas9 has been established as a genome editing platform with compact size, high accuracy, and broad targeting range, including single-AAV-deliverable adenine base editors. Here, we engineer Nme2Cas9 to further increase the activity and targeting scope of compact Nme2Cas9 base editors. We first use domain insertion to position the deaminase domain nearer the displaced DNA strand in the target-bound complex. These domain-inlaid Nme2Cas9 variants exhibit shifted editing windows and increased activity in comparison to the N-terminally fused Nme2-ABE. We next expand the editing scope by swapping the Nme2Cas9 PAM-interacting domain with that of SmuCas9, which we had previously defined as recognizing a single-cytidine PAM. We then use these enhancements to introduce therapeutically relevant edits in a variety of cell types. Finally, we validate domain-inlaid Nme2-ABEs for single-AAV delivery in vivo.

Indexed as

AdenineCRISPR-Associated Protein 9CRISPR-Cas SystemsDNAGene EditingAdenineCRISPR-Associated Protein 9DNA

Identifiers

PMID38368418
PMCPMC10874451

What OpenQuestion holds

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Registered trials

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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.