Experimental DNA- or RNA-Directed Therapies for Trinucleotide Repeat Disease

Abstract

Some repeats of three or more nucleotides in tandem, which are present in a gene or in its vicinity, tend to increase in number and for this reason are called dynamic mutations. These triplet repeats are unstable and can expand from one generation to the next. According to the expansion size, an unaffected individual can carry a pre-mutation that will expand through generations leading to the development of triplet repeat expansion diseases. The increase in the number of repeats over time leads to earlier development and increased severity of symptoms in affected individuals in successive generations. Although there is still no treatment for this type of disease, several strategies are under investigation. Here, we describe treatment approaches for triplet repeat expansion diseases that have been developed over recent years, using DNA or RNA molecules as targets. Some of these strategies have the potential for future use in gene therapy for trinucleotide repeat disorders.