ArticleMolecular therapy : the journal of the American Society of Gene Therapy2022
Reconstructed glycosylase base editors GBE2.0 with enhanced C-to-G base editing efficiency and purity.
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 26 papers.
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26 citing papers in PubMed, 33 citations in OpenAlex.
- Base editing for precision therapeutics.Cell genomics · 2026Review
- Efficient and Safe Knockout ofVeterinary sciences · 2026Article
- Research progress of base editing and prime editing tools based on the CRISPR/Cas system.Molecular therapy. Nucleic acids · 2025Review
- Gene Editing Applications as Future Cardiovascular Therapies.Annual review of genetics · 2025Review
- Advances and Applications of Plant Base Editing Technologies.International journal of molecular sciences · 2025Review
- Unraveling Etiological Indications and Therapeutic Implications of Familial Cerebral Cavernous Malformations in the Dawn of Gene Therapy for Monogenic Conditions.Current gene therapy · 2025Article
- Engineering of high-precision C-to-G base editors with expanded site selectivity and target compatibility.Nucleic acids research · 2025Article
- Synthetic evolution ofmLife · 2025Review
- Engineering miniature IscB nickase for robust base editing with broad targeting range.Nature chemical biology · 2024Article
- Glycosylase-based base editors for efficient T-to-G and C-to-G editing in mammalian cells.Nature biotechnology · 2024Article
- Gene editing therapy for cardiovascular diseases.MedComm · 2024Review
- Engineering miniature CRISPR-Cas Un1Cas12f1 for efficient base editing.Molecular therapy. Nucleic acids · 2024Article
- Development of deaminase-free T-to-S base editor and C-to-G base editor by engineered human uracil DNA glycosylase.Nature communications · 2024Article
- Article
- CRISPR/Cas9-mediated base editors and their prospects for mitochondrial genome engineering.Gene therapy · 2024Review
- Recent Research Trends in Stem Cells Using CRISPR/Cas-Based Genome Editing Methods.International journal of stem cells · 2024Review
- Breaking genetic shackles: The advance of base editing in genetic disorder treatment.Frontiers in pharmacology · 2024Review
- CRISPR base editor-based targeted random mutagenesis (BE-TRM) toolbox for directed evolution.BMB reports · 2024Review
- Precise base editing without unintended indels in human cells and mouse primary myoblasts.Experimental & molecular medicine · 2023Article
- AAV-mediated base-editing therapy ameliorates the disease phenotypes in a mouse model of retinitis pigmentosa.Nature communications · 2023Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Base editing techniques were developed for precise base conversion on cellular genomic DNA, which has great potential for the treatment of human genetic diseases. The glycosylase base editor (GBE) recently developed in our lab was used to perform C-to-G transversions in mammalian cells. To improve the application prospects of GBE, it is necessary to further increase its performance. With this aim, we replaced the human Ung in GBE with Ung1 from Saccharomyces cerevisiae. The resulting editor APOBEC-nCas9-Ung1 was tested at 17 chromosomal loci and was found to have an increased C-to-G editing efficiency ranging from 2.63% to 52.3%, with an average of 23.48%, which was a significant improvement over GBE, with an average efficiency of 15.54%, but with a decreased purity. For further improvement, we constructed APOBEC(R33A)-nCas9-Rad51-Ung1 with two beneficial modifications adapted from previous reports. This base editor was able to achieve even higher editing efficiency ranging from 8.70% to 72.1%, averaging 30.88%, while also exhibiting high C-to-G purity ranging from 35.57% to 92.92%, and was designated GBE2.0. GBE2.0 provides high C-to-G editing efficiency and purity in mammalian cells, making it a powerful genetic tool for scientific research or potential genetic therapies for disease-causing G/C mutations.
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