ArticleNature biotechnology2024
Targeted DNA integration in human cells without double-strand breaks using CRISPR-associated transposases.
Article in Nature biotechnology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.
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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.
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Who cites it
94 citing papers in PubMed, 125 citations in OpenAlex.
- Production and Storage of High-Capacity Adenoviral Vectors for the Delivery of Advanced CRISPR Systems.Methods in molecular biology (Clifton, N.J.) · 2027Article
- Genetically engineered hypoimmunogenic iPSCs: Strategies and considerations for clinical applications.Regenerative therapy · 2026Review
- Transposon end recognition and pairing by I-F3 CRISPR-associated transposase.Science advances · 2026Article
- 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
- Strategies and mechanisms of precision genome engineering: From gene editing to genome writing.iMetaOmics · 2026Review
- Transposon end recognition and excision mechanisms of type I-F CRISPR-associated transposases.Nature communications · 2026Article
- Delivering the future of immunotherapy: A state-of-the-art review of gene editing in immune cells with lipid nanoparticles.Materials today. Bio · 2026Review
- Structure and evolution-guided design of minimal RNA-guided nucleases.Science (New York, N.Y.) · 2026Article
- Structure of the Type I-F3 CAST holo integration complex reveals licensing mechanisms during RNA-guided DNA integration.bioRxiv : the preprint server for biology · 2026Article
- Retargeted serine integrases for one-step, precise integration of large DNA sequences in human cells.Nature biotechnology · 2026Article
- Optimization of IS621 recombinase/bridge RNA-directed recombination for precise insertion of large DNA fragments in human cells.Nature communications · 2026Article
- DNA remodeling couples target recognition to directional transposition in a Tn7-like CAST.bioRxiv : the preprint server for biology · 2026Article
- Programmable large-cargo integration: Overcoming size constraints for next-generation gene therapy.Synthetic and systems biotechnology · 2026Review
- Structural basis of RNA-guided DNA integration by type I CRISPR-associated transposases.bioRxiv : the preprint server for biology · 2026Article
- Non-viral targeted integration of large DNA in primary human T cells independent of double-stranded DNA breaks.Nature biomedical engineering · 2026Article
- Ultra-large targeted DNA integrations in primary human cells.bioRxiv : the preprint server for biology · 2026Article
- Developing CRISPR-Based Therapies for Epidermolysis Bullosa: A Comprehensive Review of Current Strategies.Drugs · 2026Review
- SHARK: A Specialized Host for Assembling R6K Plasmids.ACS synthetic biology · 2026Article
- Synthetic Biology of Plants and Microbes for Agriculture, Environment, and Future Applications.Chemical reviews · 2026Review
34 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
Conventional genome engineering with CRISPR-Cas9 creates double-strand breaks (DSBs) that lead to undesirable byproducts and reduce product purity. Here we report an approach for programmable integration of large DNA sequences in human cells that avoids the generation of DSBs by using Type I-F CRISPR-associated transposases (CASTs). We optimized DNA targeting by the QCascade complex through protein design and developed potent transcriptional activators by exploiting the multi-valent recruitment of the AAA+ ATPase TnsC to genomic sites targeted by QCascade. After initial detection of plasmid-based integration, we screened 15 additional CAST systems from a wide range of bacterial hosts, identified a homolog from Pseudoalteromonas that exhibits improved activity and further increased integration efficiencies. Finally, we discovered that bacterial ClpX enhances genomic integration by multiple orders of magnitude, likely by promoting active disassembly of the post-integration CAST complex, akin to its known role in Mu transposition. Our work highlights the ability to reconstitute complex, multi-component machineries in human cells and establishes a strong foundation to exploit CRISPR-associated transposases for eukaryotic genome engineering.
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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.