ideasIdea

mRNA-delivered MYC decoy proteins instead of MYC inhibitors

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.

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.

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.

What would test it

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

Who has to act

research

Cost to try

Medium ($1M to $50M)

Years to first evidence

Bottlenecks it attacks

The undruggable drivers · The proteins that drive most cancers, such as MYC, mutant p53 and most RAS variants, still have no good drug.

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mRNA-delivered MYC decoy proteins instead of MYC inhibitors

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bottlenecks