{"entity":{"id":"idea-bio1-omomyc-mrna","kind":"idea","name":"mRNA-delivered MYC decoy proteins instead of MYC inhibitors","aka":[],"tldr":"A decoy protein can bind MYC's partner and block it. Delivering the instructions for that decoy as mRNA in a fat nanoparticle avoids having to inject the protein itself.","summary":"Omomyc, a dominant-negative MYC variant, shrinks tumours in mouse models and a purified-protein version (OMO-103) has completed a first-in-human study with signs of target engagement. Protein delivery is the limitation. Encoding Omomyc-like miniproteins in lipid-nanoparticle mRNA, as used for COVID vaccines and now for intratumoural cytokines, would allow repeated dosing and tumour-biased delivery.","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":["sclc","pancreatic"],"sections":[],"technologies":["neoantigen-mrna-vaccine"],"targets":[],"drugs":[],"companies":["moderna","orna-therapeutics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-undruggable-targets"],"keyPapers":["paper-dang-nat-rev-cancer"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"LNP-mRNA expression of a MYC decoy achieves sustained nuclear expression in tumour tissue and produces at least equivalent tumour growth inhibition to purified Omomyc protein at a lower dose.","rationale":"mRNA delivery has solved manufacturing and repeat-dosing problems for other hard-to-deliver proteins; the decoy mechanism is genetically validated across many MYC-driven models.","test":"Head-to-head mouse study of LNP-mRNA decoy versus protein in MYC-driven lung and pancreatic models, with tumour and liver biodistribution and marrow toxicity as co-primary readouts.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":6},"route":"/ideas/idea-bio1-omomyc-mrna/","neighbours":{"cancer":[{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"},{"id":"sclc","kind":"cancer","name":"Small-cell lung cancer","route":"/cancers/sclc/"}],"technology":[{"id":"neoantigen-mrna-vaccine","kind":"technology","name":"Personalised neoantigen (mRNA) vaccines","route":"/technologies/neoantigen-mrna-vaccine/"}],"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/"}]}}