ArticleNature communications2021
A general theoretical framework to design base editors with reduced bystander effects.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- Beneficial bystander-enhanced cryptic splice rescue of cardiac-type Fabry GLA IVS4+919G>A by adenine base editing in patient fibroblasts.Gene therapy · 2026Article
- Constructing an Adenine Base Editor inMicroorganisms · 2026Article
- Engineering Compact Base Editors by AlphaFold-Guided Mutation Scan and Escherichia coli-Based Tri-Selection.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Algebraic formulas for first-passage times of Markov processes in the linear framework.Bulletin of mathematical biology · 2025Article
- A Novel Missense Variant of the ABCD1 Gene in X-Linked Adrenoleukodystrophy in Chinese Family.Molecular genetics & genomic medicine · 2025Article
- A side-by-side comparison of variant function measurements using deep mutational scanning and base editing.Nucleic acids research · 2025Article
- Recent advances in therapeutic gene-editing technologies.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- CRISPR: fundamental principles and implications for anaesthesia.British journal of anaesthesia · 2025Review
- Advancements of CRISPR-Mediated Base Editing in Crops and Potential Applications inInternational journal of molecular sciences · 2024Review
- A New-Generation Base Editor with an Expanded Editing Window for Microbial Cell Evolution In Vivo Based on CRISPR‒Cas12b Engineering.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- A chemically controlled Cas9 switch enables temporal modulation of diverse effectors.Nature chemical biology · 2023Article
- Base editor screens for in situ mutational scanning at scale.Molecular cell · 2023Review
- Dynamics of single-base editing: Theoretical analysis.The Journal of chemical physics · 2023Article
- Review
- Base and Prime Editing in the Retina-From Preclinical Research toward Human Clinical Trials.International journal of molecular sciences · 2022Review
- Current applications and future perspective of CRISPR/Cas9 gene editing in cancer.Molecular cancer · 2022Review
- CRISPR-based genome editing through the lens of DNA repair.Molecular cell · 2022Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Base editors (BEs) hold great potential for medical applications of gene therapy. However, high precision base editing requires BEs that can discriminate between the target base and multiple bystander bases within a narrow active window (4 - 10 nucleotides). Here, to assist in the design of these optimized editors, we propose a discrete-state stochastic approach to build an analytical model that explicitly evaluates the probabilities of editing the target base and bystanders. Combined with all-atom molecular dynamic simulations, our model reproduces the experimental data of A3A-BE3 and its variants for targeting the "TC" motif and bystander editing. Analyzing this approach, we propose several general principles that can guide the design of BEs with a reduced bystander effect. These principles are then applied to design a series of point mutations at T218 position of A3G-BEs to further reduce its bystander editing. We verify experimentally that the new mutations provide different levels of stringency on reducing the bystander editing at different genomic loci, which is consistent with our theoretical model. Thus, our study provides a computational-aided platform to assist in the scientifically-based design of BEs with reduced bystander effects.
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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.