CRISPR/CAS9 and mitochondrial gene replacement therapy: Promising techniques and ethical considerations

Sarah Fogleman, Casey Santana, Casey Bishop, Alyssa Miller, David Capco

Research output: Contribution to journalReview articlepeer-review

35 Scopus citations


Thousands of mothers are at risk of transmitting mitochondrial diseases to their offspring each year, with the most severe form of these diseases being fatal [1]. With no cure, transmission prevention is the only current hope for decreasing the disease incidence. Current methods of prevention rely on low mutant maternal mitochondrial DNA levels, while those with levels close to or above threshold (>60%) are still at a very high risk of transmission [2]. Two novel approaches may offer hope for preventing and treating mitochondrial disease: mitochondrial replacement therapy, and CRISPR/Cas9. Mitochondrial replacement therapy has emerged as a promising tool that has the potential to prevent transmission in patients with higher mutant mitochondrial loads. This method is the subject of many ethical concerns due its use of a donor embryo to transplant the patient’s nuclear DNA; however, it has ultimately been approved for use in the United Kingdom and was recently declared ethically permissible by the FDA. The leading-edge CRISPR/Cas9 technology exploits the principles of bacterial immune function to target and remove specific sequences of mutated DNA. This may have potential in treating individuals with disease caused by mutant mitochondrial DNA. As the technology progresses, it is important that the ethical considerations herein emerge and become more established. The purpose of this review is to discuss current research surrounding the procedure and efficacy of the techniques, compare the ethical concerns of each approach, and look into the future of mitochondrial gene replacement therapy.

Original languageEnglish (US)
Pages (from-to)39-52
Number of pages14
JournalAmerican Journal of Stem Cells
Issue number2
StatePublished - 2016


  • Assisted human reproduction
  • CRISPR-Cas systems
  • Ethics
  • Gene editing
  • Mitochondrial diseases
  • Mitochondrial replacement therapy
  • Nuclear transfer

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology


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