OnCo
ideasIdea

Instruct tumour cells to make antibodies against their own oncoprotein

Deliver genetic instructions so the cancer cell itself manufactures a molecule that traps its driver protein inside the cell.

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.

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.
What would test it
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
Who has to act
research
Cost to try
Medium ($1M to $50M)
Years to first evidence
9
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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