ArticleNature biomedical engineering2025
Efficient site-specific integration of large genes in mammalian cells via continuously evolved recombinases and prime editing.
Article in Nature biomedical engineering, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 135 papers, 1 of them a synthesis that pooled it.
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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
135 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- Production and Storage of High-Capacity Adenoviral Vectors for the Delivery of Advanced CRISPR Systems.Methods in molecular biology (Clifton, N.J.) · 2027Article
- Advanced gene editing technologies for oncology mechanisms, applications, and clinical implementation.Cancer gene therapy · 2026Review
- CRISPR in clinical oncology: translational advances from molecular diagnostics to therapeutics.Nature reviews. Clinical oncology · 2026Review
- Gene editing using large insertions.Nature biotechnology · 2026Article
- Article
- Beyond Precision: A Multidimensional Framework for Selecting Genetic Medicine Platforms.Cells · 2026Review
- Optimizing twin prime editing components for scalable genome editing and therapy in spinocerebellar ataxia type 3.Molecular therapy. Nucleic acids · 2026Article
- Large serine recombinase-mediated gene insertion for high-throughput screens: advantages, design principles, and applications.Nucleic acids research · 2026Review
- Programmable enzymes for targeted gene insertion.Nature reviews. Genetics · 2026Review
- Engineered genomic attachment sites for site-specific recombinases enable high-efficiency integration in plants and human cells.Nature biotechnology · 2026Article
- Writing Big in Plant Genomes: Advances, Challenges and Strategies for Targeted Large-Fragment DNA Insertion.Plant, cell & environment · 2026Review
- Article
- Advances in prime editing: Molecular innovations, Large-fragment engineering, and AI-driven design.Biodesign research · 2026Review
- Article
- Precise genomic integration of large DNA fragments by donor-directed annealing using prime editing.Nature biotechnology · 2026Article
- Donor-complementary prime editing enables precise kilobase and library-compatible DNA insertions.Nature biotechnology · 2026Article
- From Delivery to Design: Site-Specific Genome Engineering for Next-Generation CAR T-Cell Therapy.Biomedicines · 2026Review
- The use of homology-directed repair in a complex landscape of genome editors.Nature reviews. Molecular cell biology · 2026Article
- Mechanistic machine learning for prediction of prime editing outcomes.Nature biotechnology · 2026Article
75 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
Methods for the targeted integration of genes in mammalian genomes suffer from low programmability, low efficiencies or low specificities. Here we show that phage-assisted continuous evolution enhances prime-editing-assisted site-specific integrase gene editing (PASSIGE), which couples the programmability of prime editing with the ability of recombinases to precisely integrate large DNA cargoes exceeding 10 kilobases. Evolved and engineered Bxb1 recombinase variants (evoBxb1 and eeBxb1) mediated up to 60% donor integration (3.2-fold that of wild-type Bxb1) in human cell lines with pre-installed recombinase landing sites. In single-transfection experiments at safe-harbour and therapeutically relevant sites, PASSIGE with eeBxb1 led to an average targeted-gene-integration efficiencies of 23% (4.2-fold that of wild-type Bxb1). Notably, integration efficiencies exceeded 30% at multiple sites in primary human fibroblasts. PASSIGE with evoBxb1 or eeBxb1 outperformed PASTE (for 'programmable addition via site-specific targeting elements', a method that uses prime editors fused to recombinases) on average by 9.1-fold and 16-fold, respectively. PASSIGE with continuously evolved recombinases is an unusually efficient method for the targeted integration of genes in mammalian cells.
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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.