Applying Synthetic Nucleic Acid Therapeutics to Gene Activation for Haploinsufficient Diseases

Haploinsufficient autosomal dominant diseases are due to heterozygous mutations that cause inadequate protein expression. Compounds that increase expression of the wild-type allele would be one strategy for treating patients. Synthetic antisense oligonucleotides and double-stranded RNAs have the potential to increase gene expression, making them starting points for drug development. Our goal is to outline strategies for using synthetic nucleic acids to enhance gene expression. We discuss the strengths and limitations of these strategies and the practical challenges behind upregulating the expression of genes as a treatment for haploinsufficient autosomal dominant diseases.