ArticleCell discovery2023
High-efficiency targeted transgene integration via primed micro-homologues.
Article in Cell discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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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.
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Who cites it
11 citing papers in PubMed, 9 citations in OpenAlex.
- Precise genomic integration of large DNA fragments by donor-directed annealing using prime editing.Nature biotechnology · 2026Article
- Prime editing-mediated microhomology enables efficient replacement of large DNA.Nucleic acids research · 2026Article
- Article
- Non-viral targeted integration of large DNA in primary human T cells independent of double-stranded DNA breaks.Nature biomedical engineering · 2026Article
- Human Genome Safe Harbor Sites: A Comprehensive Review of Criteria, Discovery, Features, and Applications.Cells · 2026Review
- A novel carcinogenic mouse model by site-directed insertion of tandem human HRAS large DNA fragment into 15E1 site.Animal models and experimental medicine · 2025Article
- Turning "trashed" genomic loci into treasurable sites for integrating chimeric antigen receptors in T and NK cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Expanding the horizon of CAR T cell therapy: from cancer treatment to autoimmune diseases and beyond.Frontiers in immunology · 2025Review
- Current Non-Viral-Based Strategies to Manufacture CAR-T Cells.International journal of molecular sciences · 2024Review
- Recent advances in CRISPR-Cas9-based genome insertion technologies.Molecular therapy. Nucleic acids · 2024Review
- Biomaterials-mediated CRISPR/Cas9 delivery: recent challenges and opportunities in gene therapy.Frontiers in chemistry · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Due to the difficulties in precisely manipulating DNA repair pathways, high-fidelity targeted integration of large transgenes triggered by double-strand breaks is inherently inefficient. Here, we exploit prime editors to devise a robust knock-in (KI) strategy named primed micro-homologues-assisted integration (PAINT), which utilizes reverse-transcribed single-stranded micro-homologues to boost targeted KIs in different types of cells. The improved version of PAINT, designated PAINT 3.0, maximizes editing efficiency and minimizes off-target integration, especially in dealing with scarless in-frame KIs. Using PAINT 3.0, we target a reporter transgene into housekeeping genes with editing efficiencies up to 80%, more than 10-fold higher than the traditional homology-directed repair method. Moreover, the use of PAINT 3.0 to insert a 2.5-kb transgene achieves up to 85% KI frequency at several therapeutically relevant genomic loci, suggesting its potential for clinical applications. Finally, PAINT 3.0 enables high-efficiency non-viral genome targeting in primary T cells and produces functional CAR-T cells with specific tumor-killing ability. Thus, we establish that the PAINT method is a powerful gene editing tool for large transgene integrations and may open new avenues for cell and gene therapies and genome writing technologies.
Identifiers
What OpenQuestion holds
Registered trials
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.