ArticleNature biotechnology2025
Harnessing eukaryotic retroelement proteins for transgene insertion into human safe-harbor loci.
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 42 papers.
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Who cites it
42 citing papers in PubMed, 48 citations in OpenAlex.
- Discovery and engineering of avian R2 retrotransposons for all-RNA-mediated targeted DNA integration in human cells.Nature biotechnology · 2026Article
- 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
- Writing Big in Plant Genomes: Advances, Challenges and Strategies for Targeted Large-Fragment DNA Insertion.Plant, cell & environment · 2026Review
- Dynamic Proteomic and Metabolomic Analysis Reveals Metabolic Reprogramming During Early Neuronal Transdifferentiation of Human Fibroblasts Driven by Forskolin.Current issues in molecular biology · 2026Article
- 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
- Two Classes of Protein Therapeutics: Why Dose-Response Architecture Defines the Boundary of mRNA Medicines.Pharmaceutics · 2026Review
- Optimized R2 retroelement complexes for DNA insertion into plant genomes.Nature biotechnology · 2026Article
- Efficient site-specific gene addition using R2 retrotransposons in tobacco and rice.Nature biotechnology · 2026Article
- Review
- Lineage-specific evolution, structural diversity, and activity of R2 retrotransposons in animals.Genome biology · 2026Article
- Real-Time Feedback Strategically Regulates Optoelectronics for Customized Optogenetic Spinal Cord Regeneration.Exploration (Beijing, China) · 2026Article
- Single-turnover kinetic analysis of non-long terminal repeat retrotransposition defines the pathway and rate constants leading to second-strand synthesis.Nucleic acids research · 2026Article
- RAAVioli: A comprehensive approach to characterizing AAV vector integrations and rearrangements.Molecular therapy. Advances · 2026Article
- Synthetic rewriting technologies in mammalian cells.Nature communications · 2026Review
- Rewriting the genome: harnessing R2 retrotransposons for precise DNA insertion.Frontiers in genome editing · 2026Review
- R2Tg retrotransposon mediated targeted integration of exogenous genes into the 28S rDNA locus in mammalian cell lines for PKU gene therapy.Frontiers in genome editing · 2026Article
- Generation of iVero.219-mcRTA: a doxycycline-inducible high-titer KSHV producer cell line with multicopyFrontiers in cellular and infection microbiology · 2026Article
- Development of evolutionarily conserved viral integration sites as safe harbors for human gene therapy.iScience · 2025Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Current approaches for inserting autonomous transgenes into the genome, such as CRISPR-Cas9 or virus-based strategies, have limitations including low efficiency and high risk of untargeted genome mutagenesis. Here, we describe precise RNA-mediated insertion of transgenes (PRINT), an approach for site-specifically primed reverse transcription that directs transgene synthesis directly into the genome at a multicopy safe-harbor locus. PRINT uses delivery of two in vitro transcribed RNAs: messenger RNA encoding avian R2 retroelement-protein and template RNA encoding a transgene of length validated up to 4 kb. The R2 protein coordinately recognizes the target site, nicks one strand at a precise location and primes complementary DNA synthesis for stable transgene insertion. With a cultured human primary cell line, over 50% of cells can gain several 2 kb transgenes, of which more than 50% are full-length. PRINT advantages include no extragenomic DNA, limiting risk of deleterious mutagenesis and innate immune responses, and the relatively low cost, rapid production and scalability of RNA-only delivery.
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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.