Genotype-specific precision tumor therapy using mitochondrial DNA mutation-induced drug release system.

ABSTRACT: Precise killing of tumor cells without affecting surrounding normal cells is a challenge. Mitochondrial DNA (mtDNA) mutations, a common genetic variant in cancer, can directly affect metabolic homeostasis, serving as an ideal regulatory switch for precise tumor therapy. Here, we designed a mutation-induced drug release system (MIDRS), using the single-nucleotide variation (SNV) recognition ability and trans-cleavage activity of Cas12a to convert tumor-specific mtDNA mutations into a regulatory switch for intracellular drug release, realizing precise tumor cell killing. Using Ce6 as a model drug, MIDRS enabled organelle-level photodynamic therapy, triggering innate and adaptive immunity simultaneously. In vivo evaluation showed that MIDRS_MT could identify tumor tissue carrying SN

SUBMITTER: Li Y 

PROVIDER: S-EPMC10530102 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature