Evidence map›Paper›PMID 30733567›Full record

ArticleScientific reports2019

Simultaneous targeting of linked loci in mouse embryos using base editing.

Hye Kyung Lee, Michaela Willi, Harold E Smith, Shannon M Miller, David R Liu, Chengyu Liu, Lothar Hennighausen

Abstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing 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

15 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Review
  11. Review
  12. Review
  13. Review
  14. Review
  15. 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

7 authors.

Hye Kyung LeeLaboratory of Genetics and Physiology, National Institute of Diabetes and Digestive and Kidney Diseases, US National Institutes of Health, Bethesda, Maryland, 20892, USA. hyekyung.lee@nih.gov.
Michaela WilliLaboratory of Genetics and Physiology, National Institute of Diabetes and Digestive and Kidney Diseases, US National Institutes of Health, Bethesda, Maryland, 20892, USA.ORCID 0000-0002-2248-1998
Harold E SmithGenomics Core, National Institute of Diabetes and Digestive and Kidney Diseases, US National Institutes of Health, Bethesda, Maryland, 20892, USA.ORCID 0000-0002-3517-5973
Shannon M MillerMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, 02142, USA.
David R LiuMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, 02142, USA.
Chengyu LiuTransgenic Core, National Heart, Lung, and Blood Institute, US National Institutes of Health, Bethesda, Maryland, 20892, USA.
Lothar HennighausenLaboratory of Genetics and Physiology, National Institute of Diabetes and Digestive and Kidney Diseases, US National Institutes of Health, Bethesda, Maryland, 20892, USA. lotharh@niddk.nih.gov.

Funding

Transgenic CoreZICHL005907 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI LIU, CHENGYU · 2010 to 2025
$25.8M
Genetic Approaches To Understanding Organ Development and FunctionZIADK061000 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI HENNIGHAUSEN, LOTHAR · 2009 to 2025
$24.7M
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
Genomics Core FacilityZICDK071001 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI HANOVER, JOHN A. · 2009 to 2023
$16.6M
Integrating Chemistry and Evolution to Illuminate Biology and Enable Novel TherapeuticsR35GM118062 · NIGMS · HARVARD UNIVERSITY · PI LIU, DAVID R · 2016 to 2025
$6.4M
Expanding the Scope of Base EditingU01AI142756 · NIAID · BROAD INSTITUTE, INC. · PI LIU, DAVID R · 2018 to 2022
$2.1M
Howard Hughes Medical InstituteNHGRI NIH HHS RM1 HG009490NIAID NIH HHS U01 AI142756NIGMS NIH HHS R35 GM118062
6 · The paper itself

Abstract

A particular challenge in genome engineering has been the simultaneous introduction of mutations into linked (located on the same chromosome) loci. Although CRISPR/Cas9 has been widely used to mutate individual sites, its application in simultaneously targeting of linked loci is limited as multiple nearby double-stranded DNA breaks created by Cas9 routinely result in the deletion of sequences between the cleavage sites. Base editing is a newer form of genome editing that directly converts C∙G-to-T∙A, or A∙T-to-G∙C, base pairs without introducing double-stranded breaks, thus opening the possibility to generate linked mutations without disrupting the entire locus. Through the co-injection of two base editors and two sgRNAs into mouse zygotes, we introduced C∙G-to-T∙A transitions into two cytokine-sensing transcription factor binding sites separated by 9 kb. We determined that one enhancer activates the two flanking genes in mammary tissue during pregnancy and lactation. The ability to introduce linked mutations simultaneously in one step into the mammalian germline has implications for a wide range of applications, including the functional analysis of linked cis-elements creating disease models and correcting pathogenic mutations.

Indexed as

CRISPR-Cas SystemsGenetic LociAnimalsBase SequenceCytidine DeaminaseDNA Breaks, Double-StrandedEmbryo, MammalianFemaleGene EditingGenomeMaleMiceMice, Inbred C57BLMilk ProteinsMutationReceptor Activity-Modifying Protein 3Cytidine DeaminaseMilk ProteinsRamp3 protein, mouseReceptor Activity-Modifying Protein 3whey acidic proteins

Identifiers

PMID30733567
PMCPMC6367434

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.