Oligonucleotides: Right Place, Right time, Right future

RNA oligonucleotide-based drugs are a rapidly expanding category of medicines that will change the standard of care for many diseases and imminently upgrade personalized medicine in the coming years. Oligonucleotide-based therapies are demonstrating their commercial viability due to several factors: 1) a rapid design that allows almost unlimited production of molecules in record time, 2) extremely fast development times in the initial phases, going from developments between 12-21 years for traditional molecules to between 7-9 years for oligonucleotide-based therapies, 3) common and rapid chemical manufacturing processes, and finally 4) the versatility of their mechanisms of action, which allow acting on any product of any gene, and not only on cell surface or circulating proteins, as do traditional therapies.

Oligonucleotide-based therapies can specifically reduce the production of a disease-associated protein (RNAi, ASO) (1, 2), or non-conding RNA (antagomiRs) (3), or correct the reading frame of a particular messenger RNA to restore it and obtain a functional protein (Exon-Skipping ASO based strategies (2, 4). These technologies can address a wide range of hitherto untreatable “undruggable” targets and pathways, and this has contributed to their rapid acceptance and integration into industrial and pharmaceutical systems. These are therapeutic, versatile, disruptive and cross-cutting technologies. This rapid expansion is clearly seen in the high success rate of approval for these types of drugs by regulatory agencies (FDA and EMA) for rare diseases.