FAQ: How Much Do You Know About ASOs?

Antisense oligonucleotides (ASOs) are short, synthetic strands of DNA or RNA, typically 13 to 30 nucleotides long, designed to bind a complementary sequence on a target messenger RNA (mRNA) or pre-mRNA.¹ Depending on its chemistry, an ASO works through 1 of 3 mechanisms. It can recruit the enzyme RNase H1 to cleave and degrade the bound transcript, it can block a splice donor or acceptor site so the spliceosome skips a mutated exon and restores a functional reading frame, or it can sterically block ribosome binding to prevent translation without triggering RNase H activity at all.¹ Gene silencing calls for an RNase H-recruiting gapmer, restoring a disrupted protein calls for a splice-modulating chemistry such as a phosphorodiamidate morpholino oligomer (PMO) instead.¹