{"entity":{"id":"antisense-sirna","kind":"technology","name":"Oligonucleotide therapeutics","aka":[],"tldr":"Oligonucleotide therapeutics are short synthetic strands of genetic code that silence a specific cancer gene.","summary":"Oligonucleotide therapeutics are short synthetic nucleic acid strands that base-pair to a target mRNA and induce RNase H cleavage (antisense) or RISC-mediated degradation (siRNA), silencing a gene at the transcript level. In principle any gene is targetable, including undruggable transcription factors. Antisense and siRNA drugs are established outside oncology; in cancer, delivery to tumours is the barrier, since existing chemistries concentrate in the liver. Antibody-oligonucleotide conjugates and lipid nanoparticle delivery are in early trials, with targets including KRAS, STAT3, and MYC. Whether enough drug can reach solid tumours to silence a driver is the open question. The simple version is a synthetic strand of genetic code that switches off one cancer gene, if it can be delivered.","status":"phase-2","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Antisense_therapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Antisense_therapy"}],"tags":["frontier"],"related":[],"cancers":[],"sections":["targeted-therapy"],"technologies":[],"targets":[],"drugs":[],"companies":["stitchpoint-bio","isarna-therapeutics","ionis"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Base-pairing to mRNA induces RNase H cleavage or RISC-mediated degradation.","strengths":["Any gene is in principle targetable"],"limitations":["Delivery beyond liver"]},"route":"/technologies/antisense-sirna/","neighbours":{"section":[{"id":"targeted-therapy","kind":"section","name":"Targeted Therapy","route":"/fronts/targeted-therapy/"}],"company":[{"id":"achieve-life-sciences","kind":"company","name":"Achieve Life Sciences (formerly OncoGenex)","route":"/companies/achieve-life-sciences/"},{"id":"ionis","kind":"company","name":"Ionis Pharmaceuticals","route":"/companies/ionis/"},{"id":"isarna-therapeutics","kind":"company","name":"Isarna Therapeutics","route":"/companies/isarna-therapeutics/"},{"id":"stitchpoint-bio","kind":"company","name":"Stitchpoint Bio","route":"/companies/stitchpoint-bio/"}],"term":[{"id":"prostate-failed-programmes","kind":"term","name":"Prostate cancer programmes that failed, and what each failure taught","route":"/terms/prostate-failed-programmes/"},{"id":"rna","kind":"term","name":"RNA","route":"/terms/rna/"}],"drug":[{"id":"custirsen","kind":"drug","name":"Custirsen","route":"/drugs/custirsen/"},{"id":"imetelstat","kind":"drug","name":"Imetelstat","route":"/drugs/imetelstat/"}],"trial":[{"id":"affinity-custirsen","kind":"trial","name":"AFFINITY","route":"/trials/affinity-custirsen/"},{"id":"imerge","kind":"trial","name":"IMerge","route":"/trials/imerge/"},{"id":"impactmf","kind":"trial","name":"IMpactMF","route":"/trials/impactmf/"},{"id":"nct05583552","kind":"trial","name":"Study to Evaluate Imetelstat in Patients With High-Risk MDS or AML Failing HMA-based Therapy","route":"/trials/nct05583552/"},{"id":"synergy-custirsen","kind":"trial","name":"SYNERGY","route":"/trials/synergy-custirsen/"}],"technology":[{"id":"antibody-oligonucleotide-conjugates","kind":"technology","name":"Antibody-oligonucleotide conjugates","route":"/technologies/antibody-oligonucleotide-conjugates/"},{"id":"dna-origami-nanorobots","kind":"technology","name":"DNA origami nanorobots","route":"/technologies/dna-origami-nanorobots/"},{"id":"exosome-therapeutics","kind":"technology","name":"Engineered exosomes as drug carriers","route":"/technologies/exosome-therapeutics/"},{"id":"programmable-dna-targeting-therapeutics","kind":"technology","name":"Programmable DNA-targeting therapeutics","route":"/technologies/programmable-dna-targeting-therapeutics/"}],"person":[{"id":"adrian-krainer","kind":"person","name":"Adrian R. Krainer","route":"/people/adrian-krainer/"}],"bottleneck":[{"id":"b-undruggable-targets","kind":"bottleneck","name":"The undruggable drivers","route":"/bottlenecks/b-undruggable-targets/"}],"idea":[{"id":"idea-bio2-n-of-1-framework","kind":"idea","name":"A standing rulebook for one-patient treatments","route":"/ideas/idea-bio2-n-of-1-framework/"},{"id":"idea-bio1-rna-targeting-small-molecules","kind":"idea","name":"Small molecules that cut the RNA message of an undruggable oncogene","route":"/ideas/idea-bio1-rna-targeting-small-molecules/"}],"pathway":[{"id":"rna-splicing","kind":"pathway","name":"RNA splicing","route":"/pathways/rna-splicing/"}],"roadmap":[{"id":"drug-discovery-roadmap","kind":"roadmap","name":"Drug discovery roadmap: screening in mice → maps of dependency → designing in silico","route":"/roadmaps/drug-discovery-roadmap/"},{"id":"targeted-therapy-roadmap","kind":"roadmap","name":"Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall","route":"/roadmaps/targeted-therapy-roadmap/"}]}}