TAMARA MARTÍNEZ
R&D Manager, Sylentis, SAU, Madrid. Spain

Abstract

Nucleic acid-based therapeutics, have seen increased activity in the development of treatments for rare diseases due to the possibility of rational design and their shorter and cost-effective development cycles. Since the first approvals new compound approvals are occurring annually, and massive growth is expected over the next few years. The elimination of many barriers has contributed to their success. However, it is necessary to conquer new tissues to bring novel therapies to the market. The world’s production capacities are already full with the most advanced products in development and those on the market. To adapt to the market, the industry will have to deal with innovative production and sustainability constraints, which calls for the creation of cutting-edge strategies and processes.

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 ...