# mRNA-delivered MYC decoy proteins instead of MYC inhibitors

Source: https://onco.cc/ideas/idea-bio1-omomyc-mrna/  
OnCo record `idea-bio1-omomyc-mrna` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- 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.
- Proposed 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

## Sources

- Bottleneck evidence (The undruggable drivers): Dang et al., Drugging the 'undruggable' cancer targets (Nature Reviews Cancer 2017): https://doi.org/10.1038/nrc.2017.36

## Connected records

- cancers: [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/), [Small-cell lung cancer](https://onco.cc/cancers/sclc/)
- technologies: [Personalised neoantigen (mRNA) vaccines](https://onco.cc/technologies/neoantigen-mrna-vaccine/)
- companies: [Moderna](https://onco.cc/companies/moderna/), [Orna Therapeutics (Eli Lilly)](https://onco.cc/companies/orna-therapeutics/)
- bottlenecks: [The undruggable drivers](https://onco.cc/bottlenecks/b-undruggable-targets/)
- key papers: [Drugging the 'undruggable' cancer targets](https://onco.cc/key-papers/paper-dang-nat-rev-cancer/)

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