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Agresti et al. J Transl Genet Genom 2018;2:9 Journal of Translational
DOI: 10.20517/jtgg.2018.05 Genetics and Genomics

Review Open Access

MERRF and MELAS: current gene therapy trends
and approaches

Ciara Ann Agresti, Penelope Nicole Halkiadakis, Peter Tolias

Center for Healthcare Innovation and Department of Chemistry & Chemical Biology, Stevens Institute of Technology, Hoboken,
NJ 07030, USA.
Correspondence to: Dr. Peter Tolias, Center for Healthcare Innovation and Department of Chemistry & Chemical Biology, Stevens
Institute of Technology, 1 Castle Point on Hudson, Hoboken, NJ 07030, USA. E-mail: ptolias@stevens.edu
How to cite this article: Agresti CA, Halkiadakis PN, Tolias P. MERRF and MELAS: current gene therapy trends and approaches.
J Transl Genet Genom 2018;2:9. http://dx.doi.org/10.20517/jtgg.2018.05
Received: 4 Apr 2018 First Decision: 21 May 2018 Revised: 6 Jun 2018 Accepted: 12 Jun 2018 Published: 3 Jul 2018

Science Editor: Sheng-Ying Qin Copy Editor: Jun-Yao Li Production Editor: Cai-Hong Wang

Abstract
The mitochondrion is a unique organelle that predominantly functions to produce useful cellular energy in the form
of adenosine triphosphate (ATP). Unlike other non-nuclear eukaryotic organelles (with the exception of chloroplasts),
mitochondria have two lipid membranes that enclose their own mitochondrial DNA (mtDNA) and ribosomes for
protein production. Similar to nuclear DNA, mtDNA is equally susceptible to mutations that may be classified
as either pathogenic or nonpathogenic. Myoclonic Epilepsy with Ragged Red Fibers (MERRF) and Mitochondrial
Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes (MELAS) are mitochondrial diseases originating
from pathogenic point mutations located within mtDNA. Currently, there is no cure and patient care primarily
focuses on treating each disease’s associated symptoms. When considering the multiple barriers existing between
the extracellular surface of the plasma membrane and the location of the mtDNA within the mitochondrial matrix,
developing a pharmacological therapeutic that can both overcome these barriers and correct an mtDNA causing
mitochondrial disease remains difficult at best. Interestingly, the field of gene therapy may provide an opportunity
for effective therapeutic intervention by introducing a genetic payload (to a particular cellular gene) to induce the
correction. This review primarily focuses on understanding the principles of mitochondrial biology leading to the
mtDNA diseases, MERRF and MELAS, while providing a landscape perspective of gene therapy research devoted to
curing these diseases.

Keywords: Mitochondria, mitochondrial biology, mitochondrial DNA, mitochondrial diseases, gene therapy, MERRF,
A8344G, MELAS, A3243G

© The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

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