RNA- and DNA- Based Therapies for Huntington’s Disease

Excerpt

The goal of this chapter is to describe strategies for the development of RNA- and DNA-based therapies for Huntington’s disease (HD). RNA-based therapies use endogenous cellular mechanisms for the suppression of gene expression and have the potential for exquisite sequence selectivity of target genes. DNA-based therapies, notably those based on antisense technologies, are not as flexible in target selectivity but can be more stable than those derived from RNA-based silencing. Both approaches are currently being aggressively pursued with promising results in preclinical studies.

HD is a particularly attractive target for DNA- and RNA-based therapies as it is an autosomal dominant disease resulting from mutation on one allele. Thus, in concept, eliminating expression of the mutant huntingtin allele would entirely prevent the neuronal pathology that it would otherwise cause. Because the mutant huntingtin messenger RNA (mRNA) transcript would be selectively targeted, the normal transcript would remain unaffected and able to mediate the normal functions of huntingtin that may be critical for neural development and function.