Evidence map›Paper›PMID 38261981›Full record

ArticleNucleic acids research2024

Innate programmable DNA binding by CRISPR-Cas12m effectors enable efficient base editing.

Greta Bigelyte, Brigita Duchovska, Rimante Zedaveinyte, Giedrius Sasnauskas, Tomas Sinkunas, Indre Dalgediene, Giedre Tamulaitiene, Arunas Silanskas, Darius Kazlauskas, Lukas Valančauskas and 4 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
4.0field-weighted citation impact, top 6% 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

11 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
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  8. Efforts to Downsize Base Editors for Clinical Applications.International journal of molecular sciences · 2025
    Review
  9. Article
  10. Review
  11. 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

14 authors at 2 institutions in 2 countries.

Greta BigelyteInstitute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius LT-10257, Lithuania.
Brigita DuchovskaInstitute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius LT-10257, Lithuania.ORCID 0009-0006-2128-012X
Rimante ZedaveinyteInstitute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius LT-10257, Lithuania.
Giedrius SasnauskasInstitute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius LT-10257, Lithuania.
Tomas SinkunasInstitute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius LT-10257, Lithuania.ORCID 0000-0001-6004-0897
Indre DalgedieneInstitute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius LT-10257, Lithuania.
Giedre TamulaitieneInstitute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius LT-10257, Lithuania.ORCID 0000-0002-9794-3544
Arunas SilanskasInstitute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius LT-10257, Lithuania.
Darius KazlauskasInstitute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius LT-10257, Lithuania.ORCID 0000-0001-6135-8549
Lukas ValančauskasInstitute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius LT-10257, Lithuania.ORCID 0000-0002-2528-4076
Julene Madariaga-MarcosPeter Debye Institute for Soft Matter Physics, University of Leipzig, Leipzig 04103, Germany.ORCID 0000-0003-1458-3369
Ralf SeidelPeter Debye Institute for Soft Matter Physics, University of Leipzig, Leipzig 04103, Germany.ORCID 0000-0002-6642-053X
Virginijus SiksnysInstitute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius LT-10257, Lithuania.ORCID 0000-0003-1983-2096
Tautvydas KarvelisInstitute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius LT-10257, Lithuania.ORCID 0000-0002-0685-2947
Vilnius University · LTLeipzig University · DE

Funding

Central Project Management Agency, Lithuania 02-002-P-0001Lithuanian Research Library Consortium (LMBA)Research Council of Lithuania S-MIP-21-8
6 · The paper itself

Abstract

Cas9 and Cas12 nucleases of class 2 CRISPR-Cas systems provide immunity in prokaryotes through RNA-guided cleavage of foreign DNA. Here we characterize a set of compact CRISPR-Cas12m (subtype V-M) effector proteins and show that they provide protection against bacteriophages and plasmids through the targeted DNA binding rather than DNA cleavage. Biochemical assays suggest that Cas12m effectors can act as roadblocks inhibiting DNA transcription and/or replication, thereby triggering interference against invaders. Cryo-EM structure of Gordonia otitidis (Go) Cas12m ternary complex provided here reveals the structural mechanism of DNA binding ensuring interference. Harnessing GoCas12m innate ability to bind DNA target we fused it with adenine deaminase TadA-8e and showed an efficient A-to-G editing in Escherichia coli and human cells. Overall, this study expands our understanding of the functionally diverse Cas12 protein family, revealing DNA-binding dependent interference mechanism of Cas12m effectors that could be harnessed for engineering of compact base-editing tools.

Indexed as

CRISPR-Cas SystemsGene EditingDNAEndonucleasesEscherichia coliHumansPlasmidsDNAEndonucleases

Identifiers

PMID38261981
PMCPMC11013384
OpenAlexW4391126393

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.