Developing Small Activating RNA As a Therapeutic: Current Challenges and Promises

Abstract

RNA activation (RNAa) allows specific gene upregulation mediated by a small activating RNA (saRNA). Harnessing this process would help in developing novel therapeutics for undruggable diseases. Since its discovery in mid 2000s, improvements of saRNA design, synthetic chemistry and understanding of the biology have matured the way to apply RNAa. Indeed, MiNA therapeutics Ltd has conducted the first RNAa clinical trial for advanced hepatocellular carcinoma patients with promising outcomes. However, to fully realize the RNAa potential better saRNA delivery strategies are needed to target other diseases. Currently, saRNA can be delivered in vivo by lipid nanoparticles, dendrimers, lipid and polymer hybrids and aptamers. Further developing these delivery technologies and novel application of RNAa will prove to be invaluable for new treatment development.

Keywords:

• cancer treatment
• hepatocellular carcinoma
• MTL-CEBPA
• oligonucleotides
• RNA activation
• RNA delivery
• RNA therapeutics
• RNAa clinical trial
• small activating RNA

Acknowledgments

Authors would like to thank Dr CP Tan, Dr A Debacker, Dr D Vasconcelos and Dr L Sinigaglia for useful discussions.

Financial & competing interests disclosure

A Kwok and N Raulf are employees of MiNA therapeutics Ltd. N Habib is a cofounder, Head of Research and shareholder of MiNA therapeutics Ltd. N Habib is a Professor and Head of the Department of HPB Surgery at Imperial College London. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.