David R. Liu

RT @[email protected]

Today @[email protected] etal. present in @[email protected] a library of base editors #MitoKO to ablate all protein-coding genes in mouse mtDNA. #MitoKO will help generating new, clinically meaningful models for mechanistic, drug discovery and pre-clinical studies https://www.nature.com/articles/s41551-022-00968-1 1/8

🐦🔗: https://twitter.com/mito_gene/status/1599745497627267072

A library of base editors for the precise ablation of all protein-coding genes in the mouse mitochondrial genome - Nature Biomedical Engineering

A library of double-stranded-DNA deaminase-derived cytosine base editors allows for the precise ablation of every mtDNA protein-coding gene in the mouse mitochondrial genome.

Nature
Dec 5, 2022 at 12:58pmWeb
Show threadDavid R. LiuDec 5, 2022
Impressive application of DdCBEs (mitochondrial base editors) to knock out each mitochondrial gene encoding a protein in mouse cells and in mice, from Michael Minczuk’s lab @[email protected]. Should facilitate the creation of much-needed cell and animal models of mitochondrial diseases.
Show threadPhillip KyriakakisDec 5, 2022
@davidrliu I suspect knocking some out would prevent some mitochondria from replicating and the mitochondria without the base edit will continue to replicate and outcompete the knock out. I guess continuing the bases editing throughout the mouse lifetime can help mode the disease state and i think this is a great advance. But certainly not creating the ideal knock out (homoplasmy) we would hope for in a model.
Show threadPhillip KyriakakisDec 5, 2022
@davidrliu perhaps one way to prevent this would be to first encode the desired knock out in the genome flanked by LoxP such that is has a nuclear copy during the bases editing. Then once homoplasmy is achieved, recombine the nuclear copy out and use that to make the transgenic mouse. Or if making this mouse is difficult, recombine the LoxP after the mouse is made with sperm from a Cre expressing mouse (which would not donate mitochondria to the embryo). Just thinking out loud.