Anastasia Khvorova: RNAi-based Therapeutics: 2018 Outlook

A decade of progress in oligonucleotide chemistry and formulation development has resulted in several compounds, both siRNAs and antisense, demonstrating robust clinical activity. Based on sequence, these types of drugs can be designed to modulate the expression of any disease-causing gene.

Clinical utility is defined by the ability to deliver to the tissue of interest. The most promising approach is modulation of oligonucleotide delivery through direct chemical modification. Full chemical stabilization, identification of optimal conjugates (GalNAc and others), and understanding the relationship between structure and pharmacokinetic/pharmacodynamic behavior are essential to enabling sustained (many months) efficacy following a single administration.