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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749614 | PMC |
| http://dx.doi.org/10.1093/lifemedi/lnae005 | DOI Listing |
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Programmable G-to-Y base editing using engineered DNA glycosylase.
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HuidaGene Therapeutics Co., Ltd., Shanghai 200131, China.
Programmable deaminase-free base editors for G-to-Y conversion by engineered glycosylase.
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August 2023
HuidaGene Therapeutics Co., Ltd., Shanghai 200131, China.
Current DNA base editors contain nuclease and DNA deaminase that enables deamination of cytosine (C) or adenine (A), but no method for guanine (G) or thymine (T) editing is available at present. Here we developed a deaminase-free glycosylase-based guanine base editor (gGBE) with G editing ability, by fusing Cas9 nickase with engineered N-methylpurine DNA glycosylase protein (MPG). By several rounds of MPG mutagenesis via unbiased and rational screening using an intron-split EGFP reporter, we demonstrated that gGBE with engineered MPG could increase G editing efficiency by more than 1500 fold.
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