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Gene therapy in LHON
Author(s) -
VignalClermont C.,
Corral Debrinski M.,
Sahel J.A.
Publication year - 2015
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2015.0094
Subject(s) - genetic enhancement , gene , gene expression , mitochondrion , mitochondrial dna , optic neuropathy , untranslated region , vector (molecular biology) , messenger rna , biology , nuclear gene , medicine , computational biology , bioinformatics , genetics , neuroscience , optic nerve , recombinant dna
Summary Gene therapy is a promise for the treatment of Leber hereditary optic neuropathy ( LHON ). The techniques required for introducing genes into mitochondria have not yet been developed and allotopic expression is one means of circumventing this barrier. To ensure efficient mitochondrial uptake of the nuclear expressed mt DNA gene, the protein should have a mitochondrial targeting signal ( MTS ). We have optimized allotopic expression by targeting the m RNA s to the mitochondrial surface with a specific 3′UnTranslated Region ( UTR ) which can cooperate with the MTS for ensuring the localization of ND 4 m RNA to the mitochondrial surface. After having collected data proving that an AAV 2/2 vector carrying this therapeutic ND 4 gene meets the criteria of robust, long‐duration gene expression, and safety in LHON rat model and non human primate retinas, we are leading a phase I/ II , open‐label, prospective clinical trial with dose escalation, which intends to evaluate safety of this gene therapy administered in one single intravitreal ( IVT ) injection in humans with chronic ND 4 LHON . Actually 9 patients were included and no SAE or treatment‐related systemic AE occurred. At last, we look forward to be successful in the generation of a treatment for patients suffering from ND 4 LHON.