oligonucleotide therapeutic
An oligonucleotide therapeutic is a drug made from a short strand of genetic letters, the same A, C, G, T or U alphabet that spells out DNA and RNA. Instead of acting on a protein, it works further upstream by binding to a matching genetic sequence, much like one half of a zipper finding and locking onto its partner.
Because base-pairing is so specific, these short strands, usually a dozen or two letters long, can be designed on a computer to recognize one chosen RNA or DNA sequence. Depending on the chemistry, this binding can block a messenger RNA, recruit enzymes to destroy it, or alter how a gene's RNA is processed, thereby turning a disease-causing gene up or down.
Naked nucleic acids are fragile and poorly taken up by cells, so almost every oligonucleotide drug carries heavy chemical modifications to the backbone and sugars, and often a targeting tag or a lipid carrier, to survive in the body and reach the right tissue. The main families are antisense oligonucleotides, siRNA, and aptamers.
Nusinersen, an antisense oligonucleotide for spinal muscular atrophy, changes how an RNA is spliced so cells make a working protein.
A nucleic-acid drug that acts on RNA rather than on a protein.
This modality 'drugs the message' (RNA) instead of the protein, which lets it reach targets that are hard to hit with small molecules.