Allotopic expression

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Allotopic expression (AE) refers to expression of genes in the cell nucleus that normally are expressed only from the mitochondrial genome. Biomedically engineered AE has been suggested as a possible future tool in gene therapy of certain mitochondria-related diseases,[1] however this view is controversial.[2] While this type of expression has been successfully carried out in yeast, the results in mammals have been conflicting.[3]

Use in Therapy[edit]

Gensight Biologics are currently pursuing a clinical program of expressing the ND4 gene in the nucleus to prevent retinal disease.[4]

Research[edit]

The SENS Research Foundation recently reported success in expressing the ATP6 gene allotopically in vitro.[5]

As of 6 September 2016 and as a result of funds raised at lifespan.io SENS Research Foundation showed ATP6 and ATP8 could be successfully expressed and their published research appears in Nucleic Acid Research [6] providing proof of concept for the MitoSENS repair approach for repairing age related damage.

References[edit]

  1. ^ de Grey AD (September 2000). "Mitochondrial gene therapy: an arena for the biomedical use of inteins". Trends Biotechnol. 18 (9): 394–9. doi:10.1016/S0167-7799(00)01476-1. PMID 10942964. 
  2. ^ Oca-Cossio J, Kenyon L, Hao H, Moraes CT (October 2003). "Limitations of allotopic expression of mitochondrial genes in mammalian cells". Genetics. 165 (2): 707–20. PMC 1462783Freely accessible. PMID 14573482. 
  3. ^ Perales-Clemente, Ester; et al. (Jan 2011). "Allotopic expression of mitochondrial-encoded genes in mammals: achieved goal, undemonstrated mechanism or impossible task?". Nucleic Acids Res. 39 (1): 225–234. doi:10.1093/nar/gkq769. PMC 3017613Freely accessible. PMID 20823090. 
  4. ^ "Gensight". www.gensight-biologics.com. Retrieved 2016-05-20. 
  5. ^ "MitoSENS Project Results to be Published in the journal Nucleic Acids Research!". lifespan.io. 18 August 2016. Retrieved 28 November 2016. 
  6. ^ "Stable nuclear expression of ATP8 and ATP6 genes rescues a mtDNA Complex V null mutant". Nucleic Acid Research. Oxford Journals. Retrieved 28 November 2016.