Engineering mitochondrial DNA in the mouse germline using designer nuclease technology

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• Ms Beverly McCann, MRC Mitochondrial Biology Unit, University of Cambridge
• Thursday 26 April 2018, 13:10-14:00
• The Richard King Room, Darwin College.

If you have a question about this talk, please contact Lorena Escudero.

Mutations in mitochondrial DNA (mtDNA) have been linked to mitochondrial diseases. In the majority of patients affected by these diseases, the pathogenic mutation is present in a heteroplasmic state; whereby mutant and wild-type mtDNA co-exist. The proportion of mutant mtDNA dictates the penetrance and severity of the disease.  Currently there is no treatment for mitochondrial diseases. The current options to prevent transmission of diseases caused by mtDNA mutations, are genetic counseling and pre-implantation diagnosis. However, potential approaches for targeting the mutations that cause mtDNA diseases could rely upon methods of removing the mutated mtDNA, such as mitochondrial replacement techniques or selective degradation of pathogenic mtDNA by use of designer engineered nucleases. In the latter approach, DNA double strand breaks introduced by targeting pairs of mutant-specific engineered nucleases lead to degradation of the mutated mtDNA subpopulation. Using a mouse model of mitochondrial disease that harbors a heteroplasmic point mutation, we aim to selectively eliminate mutated mtDNA in mouse embryos by using mitochondrially targeted engineered nucleases. This approach could be used to prevent germline transmission of mtDNA diseases.

This talk is part of the Darwin College Science Seminars series.

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