ArticleNature biotechnology2025
Site-specific DNA insertion into the human genome with engineered recombinases.
Article in Nature biotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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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.
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
20 citing papers in PubMed.
- CRISPR-Cas and Infectious Diseases: A Decade of Translational Advances in Molecular Biotechnology.Biochemical genetics · 2026Review
- Large serine recombinase-mediated gene insertion for high-throughput screens: advantages, design principles, and applications.Nucleic acids research · 2026Review
- Programmable RNA-Guided DNA Recombination: Mechanisms, Engineering, and Applications.Biomedicines · 2026Review
- Programmable enzymes for targeted gene insertion.Nature reviews. Genetics · 2026Review
- Writing Big in Plant Genomes: Advances, Challenges and Strategies for Targeted Large-Fragment DNA Insertion.Plant, cell & environment · 2026Review
- Programming biology: next-gen AI firms raise billions to design better medicines.Nature biotechnology · 2026Article
- High-throughput editing boosts the construction of next-generation microbial cell factories.Synthetic and systems biotechnology · 2026Review
- Virus-like particles enable targeted gene engineering and pooled CRISPR screening in primary human myeloid cells.Nature biotechnology · 2026Article
- Effects of homozygous PARK7 gene mutations L166P and M26I on BNIP3/BNIP3L interactions and ER-mitochondria proximity.Biology direct · 2026Article
- Synthetic Regulatory Genomics.Annual review of genomics and human genetics · 2026Review
- In vitro properties of large serine integrase hybrids derived from ϕC31 and TG1 integrases.Nucleic acids research · 2026Article
- A guide to CAR T cell therapies: development, current status and future prospects.Nature reviews. Immunology · 2026Review
- Ultra-large targeted DNA integrations in primary human cells.bioRxiv : the preprint server for biology · 2026Article
- PE-STAR: prime editing with SOS-triggered and RecJ-augmented repair enables high-efficiency editing in Escherichia coli.Nucleic acids research · 2026Article
- Human pluripotent stem cell-derived innate and adaptive immune cells for cancer immunotherapy.Cell stem cell · 2026Review
- Functional Relevance of CASP16 Nucleic Acid Predictions as Evaluated by Structure Providers.Proteins · 2026Article
- Comprehensive profiling of activity and specificity of RNA-guided transposons reveals opportunities to engineer improved variants.Nucleic acids research · 2025Article
- Integrating Arabidopsis and crop species gene discovery for crop improvement.The Plant cell · 2025Review
- Functional relevance of CASP16 nucleic acid predictions as evaluated by structure providers.bioRxiv : the preprint server for biology · 2025Article
- Structural basis of directionality control in large serine integrases.bioRxiv : the preprint server for biology · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors.
Funding
Abstract
Insertions of large DNA sequences into the genome are broadly enabling for research and therapeutic applications. Large serine recombinases (LSRs) can mediate direct, site-specific genomic integration of multi-kilobase DNA sequences without a pre-installed landing pad, albeit with low insertion rates and high off-target activity. Here we present an engineering roadmap for jointly optimizing their DNA recombination efficiency and specificity. We combine directed evolution, structural analysis and computational models to rapidly identify additive mutational combinations. We further enhance performance through donor DNA optimization and dCas9 fusions, enabling simultaneous target and donor recruitment. Our top engineered LSR variants, superDn29-dCas9, goldDn29-dCas9 and hifiDn29-dCas9, achieve up to 53% integration efficiency and 97% genome-wide specificity at an endogenous human locus and effectively integrate large DNA cargoes up to 12 kb for stable expression in non-dividing cells, stem cells and primary human T cells. Rational engineering of DNA recombinases enables precise and efficient single-step genome insertion for diverse applications across gene and cell therapies.
Identifiers
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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.