ArticleNature communications2022
Harnessing DSB repair to promote efficient homology-dependent and -independent prime editing.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 48 citations in OpenAlex.
- Prime Editing: An Overview.Methods in molecular biology (Clifton, N.J.) · 2027Review
- Activation of Pol theta-mediated end joining begins during mitotic commitment.bioRxiv : the preprint server for biology · 2026Article
- Enhanced γ-globin reactivation and sickle cell correction through a repressor-to-activator motif switch in theMolecular therapy. Nucleic acids · 2026Article
- Advances in prime editing: Molecular innovations, Large-fragment engineering, and AI-driven design.Biodesign research · 2026Review
- Improvement of precise large-fragment deletion with a versatile nuclease prime editor.Cell discovery · 2026Article
- Optimised genome editing for precise DNA insertion and substitution using prime editors in zebrafish.eLife · 2026Article
- Prime editing in neuropsychiatric disorders: From mutation-specific target selection to clinical translation.Neuroprotection (Chichester, England) · 2026Review
- A primer on prime: A prime editing update from advances to first-in-human trial.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Review
- Enhancement of prime editing by recruiting engineered or evolved components and implementing novel strategies.Biochemistry and biophysics reports · 2026Review
- CRISPR-associated transposon for programmable viral vector engineering and prime editing.Nucleic acids research · 2026Article
- Article
- Configuration of adaptable template RNA architectures to unfold the editable space of a nuclease prime editor.Nucleic acids research · 2025Article
- Circular RNA-mediated inverse prime editing in human cells.Nature communications · 2025Article
- Dual inhibition of DNA-PK and Polϴ boosts precision of diverse prime editing systems.Nature communications · 2025Article
- Make-or-break prime editing for genome engineering in Streptococcus pneumoniae.Nature communications · 2025Article
- Modified pegRNAs mitigate scaffold-derived prime editing by-products.Nature communications · 2025Article
- Prime editing: therapeutic advances and mechanistic insights.Gene therapy · 2025Review
- Review
- Efficient in situ epitope tagging of rice genes by nuclease-mediated prime editing.The Plant cell · 2025Article
- Optimized prime editing of the Alzheimer's disease-associated APOE4 mutation.Stem cell reports · 2025Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Prime editing recently emerged as a next-generation approach for precise genome editing. Here we exploit DNA double-strand break (DSB) repair to develop two strategies that install precise genomic insertions using an SpCas9 nuclease-based prime editor (PEn). We first demonstrate that PEn coupled to a regular prime editing guide RNA (pegRNA) efficiently promotes short genomic insertions through a homology-dependent DSB repair mechanism. While PEn editing leads to increased levels of by-products, it can rescue pegRNAs that perform poorly with a nickase-based prime editor. We also present a small molecule approach that yields increased product purity of PEn editing. Next, we develop a homology-independent PEn editing strategy, which installs genomic insertions at DSBs through the non-homologous end joining pathway (NHEJ). Lastly, we show that PEn-mediated insertions at DSBs prevent Cas9-induced large chromosomal deletions and provide evidence that continuous Cas9-mediated cutting is one of the mechanisms by which Cas9-induced large deletions arise. Altogether, this work expands the current prime editing toolbox by leveraging distinct DNA repair mechanisms including NHEJ, which represents the primary pathway of DSB repair in mammalian cells.
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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.