Evidence map›Paper›PMID 39415058›Full record

ArticleNature biotechnology2025

Lung and liver editing by lipid nanoparticle delivery of a stable CRISPR-Cas9 ribonucleoprotein.

Kai Chen, Hesong Han, Sheng Zhao, Bryant Xu, Boyan Yin, Atip Lawanprasert, Marena Trinidad, Benjamin W Burgstone, Niren Murthy, Jennifer A Doudna

Erratum issuedAbstract read
In one paragraph

Article in Nature biotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 103 papers.

0numbers the graph read from it
0cells of the map it votes in
103citing 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

103 citing papers in PubMed.

  1. Article
  2. Cas12a chRDNA-mediatedMolecular therapy. Nucleic acids · 2026
    Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Review
  9. Review
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  12. Article
  13. Article
  14. Review
  15. Review
  16. Article
  17. SORT LNPs encapsulating Cas9 mRNA achieve efficient editing in skeletal muscle in a dystrophic mouse model.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  18. Review
  19. Review
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Kai Chen *Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA, USA.ORCID http://orcid.org/0000-0002-3325-3536
Hesong Han *Innovative Genomics Institute, University of California Berkeley, Berkeley, CA, USA.
Sheng ZhaoInnovative Genomics Institute, University of California Berkeley, Berkeley, CA, USA.ORCID http://orcid.org/0009-0002-9890-048X
Bryant XuDepartment of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA, USA.ORCID http://orcid.org/0009-0000-2464-6111
Boyan YinInnovative Genomics Institute, University of California Berkeley, Berkeley, CA, USA.
Atip LawanprasertInnovative Genomics Institute, University of California Berkeley, Berkeley, CA, USA.ORCID http://orcid.org/0009-0001-3163-8803
Marena TrinidadDepartment of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA, USA.
Benjamin W BurgstoneInnovative Genomics Institute, University of California Berkeley, Berkeley, CA, USA.ORCID http://orcid.org/0009-0000-8256-3867
Niren MurthyInnovative Genomics Institute, University of California Berkeley, Berkeley, CA, USA. nmurthy@berkeley.edu.ORCID http://orcid.org/0000-0002-7815-7337
Jennifer A DoudnaDepartment of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA, USA. doudna@berkeley.edu.ORCID http://orcid.org/0000-0001-9161-999X

Funding

Targeting Viroporins and Coronavirus M ProteinU19AI171110 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Nevan J Krogan · 2022 to 2026
$103.4M
Project 3U54AI170792 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Nevan J Krogan · 2022 to 2026
$35.7M
HOPE - HIV Obstruction by Programmed EpigeneticsUM1AI164559 · NIAID · J. DAVID GLADSTONE INSTITUTES · PI Lishomwa C Ndhlovu, Melanie Maria Ott · 2021 to 2026
$32.2M
Center for Genomic Editing and Recording: Development and Application of Next-Generation Genome and Epigenome Editing Methods to Advance the Study and Treatment of Human DiseaseRM1HG009490 · NHGRI · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI Brittany S. Adamson, Martin Joseph Ankrah Aryee · 2017 to 2026
$22.7M
RESEARCH PROJECT 2U19AI135990 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Nevan J Krogan · 2018 to 2026
$21.4M
Resource Core II: In Vivo CoreU19NS132303 · NINDS · UNIVERSITY OF CALIFORNIA BERKELEY · PI NIREN MURTHY · 2023 to 2026
$19.7M
Gene editing in the brain with CRISPR-PEGR01MH125979 · NIMH · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI LEE, HYE YOUNG, MURTHY, NIREN · 2021 to 2025
$3.3M
Development of a Nanoparticle-Based Gene Editing Technology for Neurological ApplicationsUG3NS115599 · NINDS · OHIO STATE UNIVERSITY · PI BANKIEWICZ, KRYSTOF S, MURTHY, NIREN · 2019 to 2021
$2.3M
Expanding CRISPR-Cas editing technology through exploration of novel Cas proteins and DNA repair systemsU01AI142817 · NIAID · UNIVERSITY OF CALIFORNIA BERKELEY · PI BANFIELD, JILLIAN, DOUDNA, JENNIFER A · 2018 to 2022
$2.0M
Development of a Nanoparticle-Based Gene Editing Technology for Neurological ApplicationsUH3NS115599 · NINDS · OHIO STATE UNIVERSITY · PI BANKIEWICZ, KRYSTOF S, MURTHY, NIREN · 2022 to 2022
$1.6M
Cas9 RNP delivery to immune cells in vivo via molecular targetingUH3AI150552 · NIAID · UNIVERSITY OF CALIFORNIA BERKELEY · PI DOUDNA, JENNIFER A, WILSON, ROSS C · 2022 to 2022
$1.3M
Targeted Delivery of Cas9 to Lung Epithelial Cells using Enveloped Delivery VehiclesR21HL173710 · NHLBI · J. DAVID GLADSTONE INSTITUTES · PI DOUDNA, JENNIFER A · 2024 to 2025
$520k
California Institute for Regenerative Medicine (CIRM) DISC2-14045California Institute for Regenerative Medicine (CIRM) DISC2-14097NHGRI NIH HHS RM1 HG009490NHLBI NIH HHS R21 HL173710NIAID NIH HHS U01 AI142817NIAID NIH HHS U19 AI135990NIAID NIH HHS U19 AI171110NIAID NIH HHS U54 AI170792NIAID NIH HHS UH3 AI150552NIAID NIH HHS UM1 AI164559NIMH NIH HHS R01 MH125979NINDS NIH HHS U19 NS132303NINDS NIH HHS UG3 NS115599NINDS NIH HHS UH3 NS115599U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01MH125979-01U.S. Department of Health & Human Services | National Institutes of Health (NIH) RM1HG009490U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) UM1AI164559
6 · The paper itself

Abstract

Lipid nanoparticle (LNP) delivery of clustered regularly interspaced short palindromic repeat (CRISPR) ribonucleoproteins (RNPs) could enable high-efficiency, low-toxicity and scalable in vivo genome editing if efficacious RNP-LNP complexes can be reliably produced. Here we engineer a thermostable Cas9 from Geobacillus stearothermophilus (GeoCas9) to generate iGeoCas9 variants capable of >100× more genome editing of cells and organs compared with the native GeoCas9 enzyme. Furthermore, iGeoCas9 RNP-LNP complexes edit a variety of cell types and induce homology-directed repair in cells receiving codelivered single-stranded DNA templates. Using tissue-selective LNP formulations, we observe genome-editing levels of 16‒37% in the liver and lungs of reporter mice that receive single intravenous injections of iGeoCas9 RNP-LNPs. In addition, iGeoCas9 RNPs complexed to biodegradable LNPs edit the disease-causing SFTPC gene in lung tissue with 19% average efficiency, representing a major improvement over genome-editing levels observed previously using viral or nonviral delivery strategies. These results show that thermostable Cas9 RNP-LNP complexes can expand the therapeutic potential of genome editing.

Indexed as

CRISPR-Associated Protein 9CRISPR-Cas SystemsGene EditingLiverLungNanoparticlesRibonucleoproteinsAnimalsHumansLipidsLiposomesMiceCRISPR-Associated Protein 9Lipid NanoparticlesLipidsLiposomesRibonucleoproteins

Identifiers

PMID39415058
PMCPMC12000389

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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.