Non-coding RNAs as therapeutic agents : The future of therapy

Abstract: Non-coding RNA (ncRNA) therapeutics are based on short oligonucleotides, both naturally occurring and artificial, which target RNA in a site-specific way to modulate gene expression. As of today, 12 synthetically produced ncRNA-based drugs are available on the market in the US and Europe, and there is a possibility of more to be approved in the near future. This project is ordered by Cytiva, a global life science company, with the aim to present an overview of the current ncRNA therapeutics field. The aim is to give Cytiva a clear indication of what type of products for oligonucleotide synthesis are requested by their clients in the pharmaceutical industry. ncRNAs were examined extensively for their potential as therapeutic agents during our literature study. Based on the number of approved drugs, clinical trials, and our overall impression of future potential, we selected the following four ncRNAs; Antisense oligonucleotides (ASOs), small interfering RNA (siRNA), microRNA (miRNA), and small nuclear RNA (snRNA). Among these, the most promising ncRNAs for therapeutic use are siRNA and ASO which usually are 20-30 nucleotides long. The most common modifications to improve drug-like properties are modifications to the backbone, sugar modifications at position 2, and methylation of nucleobases at position 5 of the oligonucleotide. In addition, ncRNA-based drugs on the market today are delivered either through non-viral mechanisms or without a delivery system. The conclusion that can be drawn from our report is the importance of being able to synthesize chemically modified ASOs and siRNA on a large scale to meet the future demand of the pharmaceutical industry.