Oligonucleotides are nucleic acid polymers with specially designed sequences, including antisense oligonucleotides (ASOs), siRNAs (small interfering RNAs), microRNAs, and aptamers. Oligonucleotides can be used to modulate gene expression through a range of processes, including RNAi, target degradation through RNase H-mediated cleavage, splicing regulation, noncoding RNA repression, gene activation, and programmed gene editing.

Most oligonucleotides (ASOs, siRNA, and microRNA) hybridize to target gene mRNA or pre-mRNA via complementary base pairing, and theoretically can selectively modulate the expression of any target gene and protein, including many “non-therapeutic” ones target. Aptamers have high affinity for the target protein, similar to the tertiary structure of antibodies, not the sequence. Oligonucleotides also offer other advantages, including relatively simple production and preparation techniques, short development cycles, and long-lasting effects.

Compared to traditional small molecule inhibitors, the use of oligonucleotides as drugs is a fundamentally novel approach. The potential of oligonucleotides in precision genetics has boosted enthusiasm for therapeutic applications in cancer, cardiovascular disease, and rare diseases. Recent FDA approvals for Givosiran, Lumasiran and Viltolarsen bring RNAi, or RNA-based therapies, into the mainstream of drug development.