Evidence map›Paper›PMID 42062564›Full record

ArticleNature biomedical engineering2026

Non-viral targeted integration of large DNA in primary human T cells independent of double-stranded DNA breaks.

Sen Fang, Na Tang, Yiyun Li, Shuyu Guo, Yangcan Chen, Xin Wang, Xueke Li, Yanping Hu, Jiawei Hao, Jun Wu and 4 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature biomedical engineering, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

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

  1. Pooled it
  2. Review
  3. Review
  4. Review
  5. Review
  6. Review
  7. Review
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.

Sen Fang *State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Na Tang *State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.ORCID http://orcid.org/0009-0007-5969-1108
Yiyun Li *State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Shuyu Guo *State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Yangcan Chen *State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Xin WangState Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Xueke LiState Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Yanping HuState Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Jiawei HaoState Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Jun WuState Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Qi ZhouState Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.ORCID http://orcid.org/0000-0002-6549-9362
Haoyi WangState Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. wanghaoyi@ioz.ac.cn.ORCID http://orcid.org/0000-0003-2135-1769
Chenxin WangState Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. wangchenxin@ioz.ac.cn.ORCID http://orcid.org/0009-0006-5240-6805
Wei LiState Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. liwei@ioz.ac.cn.ORCID http://orcid.org/0000-0001-7864-404X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Non-viral targeted integration of large DNA cargoes into human primary T cells typically requires the induction of genomic double-strand breaks (DSBs), a process associated with cytotoxicity and potential tumorigenic chromosomal abnormalities. Here we report PRIME-In, a novel genome-editing platform that uses a prime editing-engineered donor template coupled with either single (PRIME-In 1.0) or paired (PRIME-In 2.0) genomic nicks to enable precise integration of substantial DNA payloads into human cells without reliance on DSB repair pathways. Compared with traditional DSB-dependent methods, PRIME-In demonstrates markedly enhanced editing efficiency and specificity while eliminating detectable on-target and off-target chromosomal aberrations. Subsequent refinement of reagent composition and delivery protocols enabled PRIME-In-mediated engineering of primary human T cells with minimal toxicity, achieving up to 50% integration efficiency for a 3-kb CAR construct. These advances establish PRIME-In as a transformative platform for streamlining the non-viral production of genome-edited T cells, offering substantial potential for T cell-based immunotherapies.

Identifiers

PMID42062564

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.