ArticleNature communications2025
Structure and biochemistry-guided engineering of an all-RNA system for DNA insertion with R2 retrotransposons.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Diversity and genome engineering applications of R2 non-LTR retrotransposons.RNA (New York, N.Y.) · 2026Review
- Programmable enzymes for targeted gene insertion.Nature reviews. Genetics · 2026Review
- Programmable RNA-Guided DNA Recombination: Mechanisms, Engineering, and Applications.Biomedicines · 2026Review
- DNA-bound avian R2 non-LTR retrotransposon protein recruits a second R2 protein for genome-protective second-strand nicking.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Efficient site-specific gene addition using R2 retrotransposons in tobacco and rice.Nature biotechnology · 2026Article
- Optimized R2 retroelement complexes for DNA insertion into plant genomes.Nature biotechnology · 2026Article
- Review
- Fourth-generation gene editors: Integration-based genome engineering.Molecular therapy. Advances · 2026Review
- Rewriting the genome: harnessing R2 retrotransposons for precise DNA insertion.Frontiers in genome editing · 2026Review
- Transposon-derived genome editors in plants: from compact nucleases to large-fragment integration and regeneration strategies.Engineering in life sciences · 2026Review
- Molecular effects of transposable element sequences in mammalian cells.Genome biology · 2025Review
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
R2 elements, a class of non-long terminal repeat (non-LTR) retrotransposons, have the potential to be harnessed for transgene insertion. However, efforts to achieve this are limited by our understanding of the retrotransposon mechanisms. Here, we structurally and biochemically characterize R2 from Taeniopygia guttata (R2Tg). We show that R2Tg cleaves both strands of its ribosomal DNA target and binds a pseudoknotted RNA element within the R2 3' UTR to initiate target-primed reverse transcription. Guided by these insights, we engineer and characterize an all-RNA system for transgene insertion. We substantially reduce the system's size and insertion scars by eliminating unnecessary R2 sequences on the donor. We further improve the integration efficiency by chemically modifying the 5' end of the donor RNA and optimizing delivery, creating a compact system that achieves over 80% integration efficiency in several human cell lines. This work expands the genome engineering toolbox and provides mechanistic insights that will facilitate future development of R2-mediated gene insertion tools.
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Registered trials
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