Evidence map›Paper›PMID 38734692›Full record

ArticleNature communications2024

Enhancing genome editing in hPSCs through dual inhibition of DNA damage response and repair pathways.

Ju-Chan Park, Yun-Jeong Kim, Gue-Ho Hwang, Chan Young Kang, Sangsu Bae, Hyuk-Jin Cha

Erratum issuedAbstract 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. An erratum has been issued. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
–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

11 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors.

Ju-Chan Park *College of Pharmacy, Seoul National University, Seoul, Republic of Korea.ORCID http://orcid.org/0000-0001-5938-7420
Yun-Jeong Kim *College of Pharmacy, Seoul National University, Seoul, Republic of Korea.ORCID http://orcid.org/0000-0003-1863-0871
Gue-Ho HwangGenomic Medicine Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.ORCID http://orcid.org/0000-0002-4201-0974
Chan Young KangGenomic Medicine Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
Sangsu BaeGenomic Medicine Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.ORCID http://orcid.org/0000-0003-3615-8566
Hyuk-Jin ChaCollege of Pharmacy, Seoul National University, Seoul, Republic of Korea. hjcha93@snu.ac.kr.ORCID http://orcid.org/0000-0001-9277-2662

Funding

Ministry of Food and Drug Safety (MFDS) (#1475014063
6 · The paper itself

Abstract

Precise genome editing is crucial for establishing isogenic human disease models and ex vivo stem cell therapy from the patient-derived hPSCs. Unlike Cas9-mediated knock-in, cytosine base editor and prime editor achieve the desirable gene correction without inducing DNA double strand breaks. However, hPSCs possess highly active DNA repair pathways and are particularly susceptible to p53-dependent cell death. These unique characteristics impede the efficiency of gene editing in hPSCs. Here, we demonstrate that dual inhibition of p53-mediated cell death and distinct activation of the DNA damage repair system upon DNA damage by cytosine base editor or prime editor additively enhanced editing efficiency in hPSCs. The BE4stem system comprised of p53DD, a dominant negative p53, and three UNG inhibitor, engineered to specifically diminish base excision repair, improves cytosine base editor efficiency in hPSCs. Addition of dominant negative MLH1 to inhibit mismatch repair activity and p53DD in the conventional prime editor system also significantly enhances prime editor efficiency in hPSCs. Thus, combined inhibition of the distinct cellular cascades engaged in hPSCs upon gene editing could significantly enhance precise genome editing in these cells.

Indexed as

CRISPR-Cas SystemsDNA DamageDNA RepairGene EditingTumor Suppressor Protein p53Cell LineCytosineHumansMutL Protein Homolog 1CytosineMLH1 protein, humanMutL Protein Homolog 1TP53 protein, humanTumor Suppressor Protein p53

Identifiers

PMID38734692
PMCPMC11088699

What Socratic 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 Socratic graph.