Nucleic acid therapy using RNA and DNA as the active pharmaceutical ingredient (API) has the potential to cause a paradigm shift in the way diseases are addressed. This innovative therapy targets the source of the disease at the genetic level and can be used to modulate the expression of one or more proteins simultaneously – a unique advantage over conventional biologics or small molecules. Given this mode of action, RNA and DNA therapeutics are a powerful means to treat, and in some cases cure, diseases that could not be addressed by other approaches.1 RNA can be used for many applications including protein production, gene silencing and activation, enzyme replacement therapy, and gene editing. The diverse set of applications warrants the use of RNA as APIs against cancer, pulmonary diseases, metabolic diseases, gene therapy and as vaccines.
In 1998, the first therapeutic nucleic acid, a DNA oligonucleotide, was approved for clinical use. The potential of RNA as a therapeutic was made clear in 2006 when the Nobel Prize in Physiology was awarded for the discovery of gene silencing by RNA interference (RNAi), followed by the approval of the first RNAi drug in 2018.2 RNA continues to make news – this time as the approach for creating vaccines against SARS-CoV-2. Moderna, BioNTech, Curevac and many other companies are waging war against the COVID-19 pandemic, having translated the genetic sequence of the novel SARS-CoV-2 virus to messenger RNA (mRNA) vaccine candidates at record speeds. As of October 2020, there are at least 24 RNA based therapeutics and vaccines under development for COVID-19.3
Recognizing the potential of RNA-based therapeutics, this whitepaper focuses on lipid-based RNA therapeutic development.