ideasIdea

Switch off an undruggable oncogene permanently with epigenetic editing

Instead of blocking a cancer protein, add a chemical off-switch to its gene so the cell stops making it. Early versions of this tool are being tested in other diseases.

CRISPR-based epigenetic silencers (CRISPRoff and related systems) place heritable DNA methylation and repressive marks at a promoter without cutting DNA. Delivered by lipid nanoparticles, this could durably silence an amplified or overexpressed but undruggable oncogene. Epigenetic editing has entered clinical development for a liver target, establishing delivery and durability precedent in humans.

Hypothesis

A single LNP dose of an epigenetic silencer targeting an amplified oncogene achieves durable transcript suppression in tumour tissue for more than four weeks and inhibits tumour growth.

Rationale

Silencing avoids the need for a binding pocket entirely, and heritable repression means dividing tumour cells retain the off state. Tumour-selective delivery remains the main risk.

What would test it

In a MYCN-amplified neuroblastoma model, compare tumour and liver transcript silencing and durability after systemic LNP dosing, with methylation sequencing to confirm mechanism and off-target promoter analysis.

Maturity

speculative

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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Switch off an undruggable oncogene permanently with epigenetic editing

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cancers

technologies

bottlenecks