Figure 1.

Methods of reducing mtDNAs harboring mutations to treat misregulation of mitochondrial gene expression. (A) Nuclease cleaves the target mutated sites. (B) ZFN: constructed by fusing the Fok I endonuclease with an array of zinc fingers, each having a recognition ability for a three-base DNA sequence. (C) TALEN: constructed by fusing Fok I with single base-recognizing domains, TALEs. (D) CRISPR: gRNA recognizes the mutation-including domain, and Cas9 cleaves mtDNA around the gRNA-bound site. (E) DdCBE: TALEs recognize the periphery of the mutation, and the two parts of DddA were fused to form the whole DddA toxin that can convert cytosine to thymidine.