Allotopic expression

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

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

Research

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 Acids Research [6] providing proof of concept for the MitoSENS repair approach for repairing age related damage.

References

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.
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 1462783. PMID 14573482.
Perales-Clemente, Ester; et al. (January 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 3017613. PMID 20823090.
"Gensight". www.gensight-biologics.com. Retrieved 20 May 2016.
"MitoSENS Project Results to be Published in the journal Nucleic Acids Research!". lifespan.io. 18 August 2016. Retrieved 28 November 2016.
"Stable nuclear expression of ATP8 and ATP6 genes rescues a mtDNA Complex V null mutant". Nucleic Acids Research. Oxford Journals. Retrieved 28 November 2016.

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[1] 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 1462783. PMID 14573482.

[3] Perales-Clemente, Ester; et al. (January 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 3017613. PMID 20823090.

[4] "Gensight". www.gensight-biologics.com. Retrieved 20 May 2016.

[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 Acids Research. Oxford Journals. Retrieved 28 November 2016.