Quadruple pegRNA enables programmable and efficient large genomic insertion

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Quadruple pegRNA enables programmable and efficient large genomic insertion

Anzalone, A. V. et al. Search-and-replace genome editing without double-strand breaks or donor DNA. Nature 576 , 149–157 (2019). Article CAS PubMed PubMed Central ADS Google Scholar Anzalone, A. V. …

Anzalone, A. V. et al. Search-and-replace genome editing without double-strand breaks or donor DNA. Nature 576 , 149–157 (2019). Article CAS PubMed PubMed Central ADS Google Scholar Anzalone, A. V. et al. Programmable deletion, replacement, integration and inversion of large DNA sequences with twin prime editing. Nat. Biotechnol. 40 , 731–740 (2022). Article CAS PubMed Google Scholar Wang, J. et al. Efficient targeted insertion of large DNA fragments without DNA donors. Nat. Methods 19 , 331–340 (2022). Article CAS PubMed Google Scholar Yarnall, M. T. N. et al. Drag-and-drop genome insertion of large sequences without double-strand DNA cleavage using CRISPR-directed integrases. Nat. Biotechnol. 41 , 500–512 (2023). Article CAS PubMed Google Scholar Pandey, S. et al. Efficient site-specific integration of large genes in mammalian cells via continuously evolved recombinases and prime editing. Nat. Biomed. Eng. 9 , 22–39 (2025). Article CAS PubMed Google Scholar Witte, I. P. et al. Programmable gene insertion in human cells with a laboratory-evolved CRISPR-associated transposase. Science 388 , eadt5199 (2025). Article CAS PubMed PubMed Central Google Scholar Komor, A. C., Kim, Y. B., Packer, M. S., Zuris, J. A. & Liu, D. R. Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage. Nature 533 , 420–424 (2016). Article CAS PubMed PubMed Central ADS Google Scholar Gaudelli, N. M. et al. …

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