Mitochondrial replacement therapy aims to prevent genetic disorders by transferring mitochondria from a donor egg to one with mutations in the mitochondrial DNA. This technique allows for the inheritance of healthy mitochondrial DNA instead of disease-causing mutations. Preclinical animal studies have shown this therapy to be safe and effective, with donor mitochondrial DNA being passed down to subsequent generations. It represents the first form of germline gene therapy for inherited mitochondrial diseases.

1. MITOCHONDRIAL REPLACEMENT THERAPY
Shoukhrat Mitalipov
Center for Embryonic Cell and Gene Therapy

2.  10,000 gene mutations causing human disease
 Vast majority of genetic disorders are inherited
(germline) and can be passed down to children
 Palliative treatments, no cure
 Somatic gene therapy is limited (too late, too many cells
to target, impossible to reach in vivo, limited DNA repair
capacity, does not prevent transmission to children, etc.)
 Ultimate goal is to prevent genetic disorders!
Heritable Diseases

3. mtDNA disease Inheritance
Peter Braude
2015 Summit on Human Gene Editing

4. Mitochondrial Replacement Therapy
Spindle Transfer between MII oocytes
Tachibana et al., Nature, 2009
Kang et al., Nature, 2016

5. Polar body 1 transfer
Ma et al., Cell Stem Cell, 2016

6. Mito & TrackerTachibana et al., Nature, 2009

7. Germline transmission of donor mtDNA to
F2 offspring
Van Dyken et al., unpublished

8. MRT Highlights
 Use of mtDNA from donor egg (not recombinant)
 Applicable to any mtDNA mutation type
 Preclinical animal studies demonstrate safety and
efficacy
 First form of germline gene therapy