ArticleMolecular therapy : the journal of the American Society of Gene Therapy2022
Eliminating predictable DNA off-target effects of cytosine base editor by using dual guiders including sgRNA and TALE.
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 9 papers.
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Who cites it
9 citing papers in PubMed.
- DNA and RNA editing for the therapy of human diseases: current status, challenges, and future prospects.Molecular biomedicine · 2026Review
- Research progress of base editing and prime editing tools based on the CRISPR/Cas system.Molecular therapy. Nucleic acids · 2025Review
- Base and Prime Editing for Inherited Retinal Diseases: Delivery Platforms, Safety, Efficacy, and Translational Perspectives.Pharmaceutics · 2025Review
- Gene mutation estimations via mutual information and Ewens sampling based CNN & machine learning algorithms.Journal of applied statistics · 2025Article
- Mini-PE, a prime editor with compact Cas9 and truncated reverse transcriptase.Molecular therapy. Nucleic acids · 2023Article
- Bioinformatic and literature assessment of toxicity and allergenicity of a CRISPR-Cas9 engineered gene drive to control Anopheles gambiae the mosquito vector of human malaria.Malaria journal · 2023Article
- Base editors: development and applications in biomedicine.Frontiers of medicine · 2023Review
- Gene editing innovations and their applications in cardiomyopathy research.Disease models & mechanisms · 2023Review
- Article
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Authors and funding
20 authors.
Funding
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Abstract
Predictable DNA off-target effect is one of the major safety concerns for the application of cytosine base editors (CBEs). To eliminate Cas9-dependent DNA off-target effects, we designed a novel effective CBE system with dual guiders by combining CRISPR with transcription activator-like effector (TALE). In this system, Cas9 nickase (nCas9) and cytosine deaminase are guided to the same target site to conduct base editing by single-guide RNA (sgRNA) and TALE, respectively. However, if nCas9 is guided to a wrong site by sgRNA, it will not generate base editing due to the absence of deaminase. Similarly, when deaminase is guided to a wrong site by TALE, base editing will not occur due to the absence of single-stranded DNA. In this way, Cas9- and TALE-dependent DNA off-target effects could be completely eliminated. Furthermore, by fusing TALE with YE1, a cytidine deaminase with minimal Cas9-independent off-target effect, we established a novel CBE that could induce efficient C-to-T conversion without detectable Cas9- or TALE-dependent DNA off-target mutations.
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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.