McKnight Building 404 (D880)
John Guy, M.D.
- The Rodgers Research Chair in Ophthalmology
Somatic and germline mtDNA mutations have been reported for a wide variety of cancers. These include renal adenocarcinoma, colon cancer cells, head and neck tumours, astrocytic tumours, thyroid tumours, breast tumours, ovarian tumours, prostate and bladder cancer, neuroblastomas and oncocytomas. The identification of clearly deleterious mtDNA mutations in cancer tissues, such as an intragenic deletion or the common tRNALeu(UUR) A3243G MELAS mutation validate the relevance of pathogenic mutations in neoplastic transformation. The importance of the mtDNA in cancer has been confirmed by the exchange of cancer cell mtDNA with pathogenic or normal mtDNA, resulting in alterations of cancer cell phenotypes. However, the strategy to correct the mtDNA mutation is inadequate, because of no procedure is thus far available for introduction of exogenous DNAs into mitochondria in living cells or even into isolated mitochondria. Dr. Guy and his group have developed a novel technology to redirect the adeno associated virus (AAV) virion to mitochondria rather than to its typical target, the nucleus, by addition of a mitochondrial targeting sequence (MTS) to the capsid, the protein shell of the virus and used it deliver mtDNA directly to mitochondria in adult mouse by using intraocular injection or mouse fertilized eggs by using microinjection. This innovative technology has implications for treating the cancer with gene therapy by bringing the mitochondrial bioenergetics and metabolism back to the normal level and preventing cells from initiating and /or sustaining the transformed state.