Miniature genome editors derived from engineering Cas9 ancestor
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ABSTRACT
Miniature genome editors are highly desirable for gene therapy by facilitating in vivo delivery via single adeno-associated virus (AAV) vector. Recently, a group of hypercompact endonuclease named as IscB with only ~500 aa is found to be the ancestry proteins of Cas9. However, IscB exhibited only marginal genome editing activity in human cells. Our study published in Nature Methods on May 25th, 2023 reported successfully improving the genome editing activity of IscB as efficient as Cas9. Fusion of our enhanced IscB with T5 exonuclease further boost the editing efficiency while decreased the risk of inducing chromosomal translocation. Importantly, two miniature base editors generated by fusing the enhanced IscB variant with deaminase also showed markedly high efficiency for C-to-T and A-to-G editing in human cells. Overall, these findings serve as a good basis for the community to take advantage of miniature IscB for gene editing therapy with single AAV. -
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REFERENCES
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Zhou Y. and Xu C. (2023). Miniature genome editors derived from engineering Cas9 ancestor. The Innovation Life 1(1), 100008. https://doi.org/10.59717/j.xinn-life.2023.100008
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Zhou Y. and Xu C. (2023). Miniature genome editors derived from engineering Cas9 ancestor. The Innovation Life 1(1), 100008. https://doi.org/10.59717/j.xinn-life.2023.100008
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Figure 1.
Engineering miniature genome editors from IscB
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