Pharmaceutical Research

, Volume 24, Issue 2, pp 228–238 | Cite as

Gene Therapy of the Other Genome: The Challenges of Treating Mitochondrial DNA Defects

  • Gerard G. M. D’Souza
  • Sarathi V. Boddapati
  • Volkmar WeissigEmail author
Research Paper


Human mitochondrial DNA is a 16.5 kb circular DNA molecule located inside the mitochondrial matrix. Although accounting for only about 1% of total cellular DNA, defects in mitochondrial DNA have been found to have major effects on human health. A single mtDNA mutation may cause a bewildering variety of clinical symptoms mainly involving the neuromuscular system at any age of onset. Despite significant advances in the understanding of mitochondrial DNA defects at a molecular level, the clinical diagnosis of mtDNA diseases remains a significant challenge and effective therapies for such diseases are as yet unavailable. In contrast to gene therapy for chromosomal DNA defects, mitochondrial gene therapy is a field that is still in its infancy and attempts towards gene therapy of the mitochondrial genome are rare. In this review we outline what we believe are the unique challenges associated with the correction of mtDNA mutations and summarize current approaches to gene therapy for the “other genome”.

Key words

delocalized cations DQAsomes gene therapy liposomes mitochondria mitochondrial DNA delivery mitochondrial targeting nonviral vectors 



The authors are grateful for funding received over the past 5 years from the Muscular Dystrophy Association (Tucson, AZ), the United Mitochondrial Disease Foundation (Pittsburgh, PA) and from Northeastern University (Boston, MA).


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Copyright information

© Springer Science+Business Media, LLC 2006

Authors and Affiliations

  • Gerard G. M. D’Souza
    • 1
  • Sarathi V. Boddapati
    • 1
  • Volkmar Weissig
    • 1
    Email author
  1. 1.Bouvé College of Health Sciences, Department of Pharmaceutical SciencesNortheastern UniversityBostonUSA

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