Cell type-selective targeting by heterobifunctional protein binders via in-cell enrichment.

Heterobifunctional protein binders achieve cell-type-specific targeting with subnanomolar potency via FKBP12-dependent enrichment.

• Why it matters: Expanding therapeutic options requires precise targeting of specific cell types, especially when closely related proteins are involved, to minimize off-target effects and improve efficacy.
• What they did: The study systematically designed bifunctional molecules using FKBP12 as a presenter protein and tested their ability to selectively kill certain cell types and differentiate between similar bromodomains, demonstrating the "CellTrap" mechanism.
• The result: This approach enables highly selective, potent cell targeting by leveraging abundant, non-essential proteins like FKBP12, paving the way for more precise and effective therapeutic strategies.