{"entity":{"id":"idea-bio1-mrna-intrabodies","kind":"idea","name":"Instruct tumour cells to make antibodies against their own oncoprotein","aka":[],"tldr":"Deliver genetic instructions so the cancer cell itself manufactures a molecule that traps its driver protein inside the cell.","summary":"Intrabodies (single-domain antibodies or designed binders expressed intracellularly) can sequester or degrade targets that small molecules cannot reach. mRNA-LNP delivery makes transient intracellular expression feasible without viral vectors, and fusion to a degron converts binding into destruction. Delivery specificity and expression level are the open questions rather than the biology.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The undruggable drivers): Dang et al., Drugging the 'undruggable' cancer targets (Nature Reviews Cancer 2017)","url":"https://doi.org/10.1038/nrc.2017.36"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["neoantigen-mrna-vaccine","protac-degrader"],"targets":[],"drugs":[],"companies":["orna-therapeutics","moderna"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-undruggable-targets"],"keyPapers":["paper-dang-nat-rev-cancer"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"An mRNA-encoded degron-fused intrabody reduces its intracellular oncoprotein target by more than 60 percent in tumour tissue and inhibits growth in a xenograft after repeated dosing.","rationale":"Intrabody function is well established in cell culture; mRNA delivery has solved the manufacturing problem for intracellular proteins in other indications, and antibody-like binders can be raised against surfaces no small molecule can address.","test":"Mouse study comparing tumour and liver expression, target degradation and growth inhibition for an mRNA intrabody against a validated intracellular driver, with immunogenicity monitoring on repeat dosing.","maturity":"speculative","actor":"research","cost":"medium","horizonYears":9},"route":"/ideas/idea-bio1-mrna-intrabodies/","neighbours":{"technology":[{"id":"neoantigen-mrna-vaccine","kind":"technology","name":"Personalised neoantigen (mRNA) vaccines","route":"/technologies/neoantigen-mrna-vaccine/"},{"id":"protac-degrader","kind":"technology","name":"PROTACs & molecular glues (targeted protein degradation)","route":"/technologies/protac-degrader/"}],"company":[{"id":"moderna","kind":"company","name":"Moderna","route":"/companies/moderna/"},{"id":"orna-therapeutics","kind":"company","name":"Orna Therapeutics (Eli Lilly)","route":"/companies/orna-therapeutics/"}],"bottleneck":[{"id":"b-undruggable-targets","kind":"bottleneck","name":"The undruggable drivers","route":"/bottlenecks/b-undruggable-targets/"}],"paper":[{"id":"paper-dang-nat-rev-cancer","kind":"paper","name":"Drugging the 'undruggable' cancer targets","route":"/key-papers/paper-dang-nat-rev-cancer/"}]}}