Mitochondrial-Targeted Gene Therapy for Treating Cancer
Although mitochondria are targeted in cancer, current strategies to specifically and effectively destroy cancer mitochondria in vivo are limited.
The researchers developed mitochondrial luminoptogenetics (mLumiOpto), designed to directly disrupt the inner mitochondrial membrane potential and induce cancer cell death.
The mLumiOpto genes were selectively delivered to cancer cells in vivo by an adeno-associated virus carrying a cancer-specific promoter or cancer-targeted mAB-tagged exosome-associated adeno-associated virus.
When activated, cancer cell mitochondrial depolarization is triggered and subsequent cell death and has shown remarkable efficacy in reducing tumor burden and killing tumor cells in glioblastoma and triple-negative breast cancer xenograft mouse models.
The approach also induces antitumor immune response, increasing infiltration of dendritic cells and CD8+ T cells in the tumor microenvironment.
https://aacrjournals.org/cancerres/article/84/23/4049/750183/mLumiOpto-Is-a-Mitochondrial-Targeted-Gene-Therapy
