Possibility of genetic restoration for a disease treatment

Abstract

We are trying to alter the coded message of RNA transcripts by photochemical RNA editing to treat genetic diseases. A mutation of mtDNA T8993C in Leigh syndrome as a model, we subjected site-directed deamination of C to U by reversible photoligation using hairpin-type oligonucleotides with carboxyvinyldeoxy-uridine at the 5'-terminal. We observed significant objective base substituted fragment with ODN2 as a 72mer ODN as a target. Then, we tried to genetic restoration experiments as patient derived samples as targets. ODN2 could restore 10% of the mutated C to U, when in-vitro-synthesized-full-length RNA was used as a target. Moreover, the site-directed deamination was performed even toward total RNA from the patients's cells as a target.