Journal of Bioenergetics and Biomembranes

, Volume 36, Issue 4, pp 387–393 | Cite as

Development of Mitochondrial Gene Replacement Therapy

  • Shaharyar M. Khan
  • James P. BennettJr.


Many “classic” mitochondrial diseases have been described that arise from single homoplasmic mutations in mitochondrial DNA (mtDNA). These diseases typically affect nonmitotic tissues (brain, retina, muscle), present with variable phenotypes, can appear sporadically, and are untreatable. Evolving evidence implicates mtDNA abnormalities in diseases such as Alzheimer's, Parkinson's, and type II diabetes, but specific causal mutations for these conditions remain to be defined. Understanding the mtDNA genotype–phenotype relationships and developing specific treatment for mtDNA-based diseases is hampered by inability to manipulate the mitochondrial genome. We present a novel protein transduction technology (“protofection”) that allows insertion and expression of the human mitochondrial genome into mitochondria of living cells. With protofection, the mitochondrial genotype can be altered, or exogenous genes can be introduced to be expressed and either retained in mitochondria or be directed to other organelles. Protofection also delivers mtDNA in vivo, opening the way to rational development of mitochondrial gene replacement therapy of mtDNA-based diseases.

Mitochondria mitochondrial DNA protein transduction mitochondrial genome 


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Copyright information

© Springer Science+Business Media, Inc. 2004

Authors and Affiliations

  • Shaharyar M. Khan
    • 1
    • 2
  • James P. BennettJr.
    • 1
  1. 1.Center for the Study of Neurodegenerative DiseasesUniversity of VirginiaCharlottesvilleVirginia
  2. 2.GENCIA CorporationCharlottesvilleVirginia

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