ArticleMolecular therapy : the journal of the American Society of Gene Therapy2022
A flexible split prime editor using truncated reverse transcriptase improves dual-AAV delivery in mouse liver.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 1 of them a synthesis that pooled it.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
79 citing papers in PubMed, 1 synthesis or guideline pooled it, 106 citations in OpenAlex.
- Pooled it
- Efficient PE system PE7-scFv-MLH1dn by optimizing the configuration of La and MLH1dn.Synthetic and systems biotechnology · 2026Article
- Dense RNA motif modifications enable robust in vivo prime editing and enhance efficiencies of diverse editing systems.Nature biomedical engineering · 2026Article
- Advances in prime editing: Molecular innovations, Large-fragment engineering, and AI-driven design.Biodesign research · 2026Review
- Review
- Application of CRISPR-Cas9-Based Gene Editing Technology in Inherited Liver Diseases.International journal of molecular sciences · 2026Review
- The future of pediatric gene therapy: CRISPR-Cas9, AI, and personalized medicine.Pediatric research · 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
- Programmable large-cargo integration: Overcoming size constraints for next-generation gene therapy.Synthetic and systems biotechnology · 2026Review
- Prime editing: Emerging mechanisms, engineering innovations, and next-generation applications.Biodesign research · 2026Review
- Article
- Gene-sized editing for the therapy of genetic diseases.Functional & integrative genomics · 2026Review
- CRISPR-Cas editing technologies for viral-mediated gene therapies of human diseases: Mechanisms, progress, and challenges.Molecular therapy. Nucleic acids · 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
- Coiled-coil heterodimer-mediated split base editing systems enable flexible and robust nucleotide substitutions.Nature communications · 2026Article
- The reverse transcriptase domain of prime editors contributes to DNA repair in mammalian cells.Nature biotechnology · 2026Article
- Research progress of base editing and prime editing tools based on the CRISPR/Cas system.Molecular therapy. Nucleic acids · 2025Review
- The multiple layers of RNA response in double-strand break repair.Experimental & molecular medicine · 2025Review
- Base and Prime Editing for Inherited Retinal Diseases: Delivery Platforms, Safety, Efficacy, and Translational Perspectives.Pharmaceutics · 2025Review
19 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Prime editor (PE) has tremendous promise for gene therapy. However, it remains a challenge to deliver PE (>6.3 kb) in vivo. Although PE can be split into two fragments and delivered using dual adeno-associated viruses (AAVs), choice of split sites within Cas9-which affects editing efficiency-is limited due to the large size of PE. Furthermore, overexpressing reverse transcriptase in mammalian cells might disrupt translation termination via its RNase H domain. Here, we developed a compact PE without the RNase H domain that showed editing comparable with full-length PE. With compact PE, we used a Cas9 split site (Glu 573) that supported robust editing in cells (up to 93% of full-length PE) and in mouse liver. We then demonstrated that split-cPE573 delivered by dual-AAV8 efficiently mediated a 3-bp TGA insertion in the Pcsk9 gene in mouse liver. Compact PE without the RNase H domain abolished its binding to peptidyl release factor 1 (eRF1) and mitigated the stop codon readthrough effect observed with full-length PE. This study identifies a compact PE with a flexible split design to advance utility of prime editing in vivo.
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What OpenQuestion holds
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.