Mitochondrial Genome Engineering: The Revolution May Not Be CRISPR-Ized

Payam A. Gammage, Carlos T. Moraes, Michal Minczuk

Research output: Contribution to journalReview article

56 Scopus citations

Abstract

In recent years mitochondrial DNA (mtDNA) has transitioned to greater prominence across diverse areas of biology and medicine. The recognition of mitochondria as a major biochemical hub, contributions of mitochondrial dysfunction to various diseases, and several high-profile attempts to prevent hereditary mtDNA disease through mitochondrial replacement therapy have roused interest in the organellar genome. Subsequently, attempts to manipulate mtDNA have been galvanized, although with few robust advances and much controversy. Re-engineered protein-only nucleases such as mtZFN and mitoTALEN function effectively in mammalian mitochondria, although efficient delivery of nucleic acids into the organelle remains elusive. Such an achievement, in concert with a mitochondria-adapted CRISPR/Cas9 platform, could prompt a revolution in mitochondrial genome engineering and biological understanding. However, the existence of an endogenous mechanism for nucleic acid import into mammalian mitochondria, a prerequisite for mitochondrial CRISPR/Cas9 gene editing, remains controversial.

Original languageEnglish (US)
Pages (from-to)101-110
Number of pages10
JournalTrends in Genetics
Volume34
Issue number2
DOIs
StatePublished - Feb 2018

Keywords

  • CRISPR/Cas9
  • RNA import
  • mitoTALEN
  • mitochondria
  • mtDNA
  • mtZFN

ASJC Scopus subject areas

  • Genetics

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