Targeted A-to-G base editing in human mitochondrial DNA with programmable deaminases, 2022, Cho et al

JohnTheJack · Apr 26, 2022

SUMMARY
Mitochondrial DNA (mtDNA) editing paves the way for disease modeling of mitochondrial genetic disorders in cell lines and animals and also for the treatment of these diseases in the future.

Bacterial cytidine deaminase DddA-derived cytosine base editors (DdCBEs) enabling mtDNA editing, however, are largely limited to C-to-T conversions in the 50 -TC context (e.g., TC-to-TT conversions), suitable for generating merely 1/8 of all possible transition (purine-to-purine and pyrimidine-to-pyrimidine) mutations.

Here, we present transcription-activator-like effector (TALE)-linked deaminases (TALEDs), composed of custom-designed TALE DNA-binding arrays, a catalytically impaired, full-length DddA variant or split DddA originated from Burkholderia cenocepacia, and an engineered deoxyadenosine deaminase derived from the E. coli TadA protein, which induce targeted A-to-G editing in human mitochondria.

Custom-designed TALEDs were highly efficient
in human cells, catalyzing A-to-G conversions at a total of 17 target sites in various mitochondrial genes with editing frequencies of up to 49%.
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Direct link to PDF:
https://www.cell.com/cell/pdf/S0092-8674(22)00389-0.pdf

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Targeted A-to-G base editing in human mitochondrial DNA with programmable deaminases, 2022, Cho et al

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Targeted A-to-G base editing in human mitochondrial DNA with programmable deaminases, 2022, Cho et al

JohnTheJack Moderator Staff Member

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