Evidence map›Paper›PMID 38453904›Full record

ArticleNature communications2024

Enhancing prime editor activity by directed protein evolution in yeast.

Yanik Weber, Desirée Böck, Anastasia Ivașcu, Nicolas Mathis, Tanja Rothgangl, Eleonora I Ioannidi, Alex C Blaudt, Lisa Tidecks, Máté Vadovics, Hiromi Muramatsu and 6 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 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing 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

18 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Article
  5. A primer on prime: A prime editing update from advances to first-in-human trial.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Review
  6. Review
  7. Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Review
  16. MutaT7ACS synthetic biology · 2024
    Article
  17. Article
  18. 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

16 authors.

Yanik WeberInstitute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland.
Desirée BöckInstitute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland.ORCID 0000-0001-8142-0629
Anastasia IvașcuDepartment of Biochemistry, University of Zurich, Zurich, Switzerland.
Nicolas MathisInstitute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland.ORCID 0000-0002-4051-8344
Tanja RothganglInstitute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland.ORCID 0000-0001-7799-2413
Eleonora I IoannidiInstitute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland.
Alex C BlaudtDepartment of Biochemistry, University of Zurich, Zurich, Switzerland.
Lisa TidecksInstitute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland.
Máté VadovicsDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Hiromi MuramatsuDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0003-1544-1493
Andreas ReichmuthInstitute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland.
Kim F MarquartInstitute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland.ORCID 0000-0001-7393-4398
Lucas KisslingInstitute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland.ORCID 0000-0002-4989-0695
Norbert PardiDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0003-1008-6242
Martin JinekDepartment of Biochemistry, University of Zurich, Zurich, Switzerland.ORCID 0000-0002-7601-210X
Gerald SchwankInstitute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland. schwank@pharma.uzh.ch.ORCID 0000-0003-0767-2953

Funding

Lipid nanoparticles as novel adjuvants inducing effective T follicular helper cell and humoral immune responsesR01AI153064 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Michela Locci, Norbert Pardi · 2020 to 2026
$4.2M
NIAID NIH HHS R01 AI153064
6 · The paper itself

Abstract

Prime editing is a highly versatile genome editing technology that enables the introduction of base substitutions, insertions, and deletions. However, compared to traditional Cas9 nucleases prime editors (PEs) are less active. In this study we use OrthoRep, a yeast-based platform for directed protein evolution, to enhance the editing efficiency of PEs. After several rounds of evolution with increased selection pressure, we identify multiple mutations that have a positive effect on PE activity in yeast cells and in biochemical assays. Combining the two most effective mutations - the A259D amino acid substitution in nCas9 and the K445T substitution in M-MLV RT - results in the variant PE_Y18. Delivery of PE_Y18, encoded on DNA, mRNA or as a ribonucleoprotein complex into mammalian cell lines increases editing rates up to 3.5-fold compared to PEmax. In addition, PE_Y18 supports higher prime editing rates when delivered in vivo into the liver or brain. Our study demonstrates proof-of-concept for the application of OrthoRep to optimize genome editing tools in eukaryotic cells.

Indexed as

Biological AssaySaccharomyces cerevisiaeAmino Acid SubstitutionAnimalsBrainCell LineCRISPR-Cas SystemsMammals

Identifiers

PMID38453904
PMCPMC10920827

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.