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<p>Chemically induced proximity (CIP) has remarkably advanced the development of molecular and cellular therapeutics. To maximize therapeutic potential, there is a pressing need to expand the repertoire of CIP systems of translational values, favoring chemical ligands that are cost-effective, structurally simple, biocompatible, reversible and have minimal side effects. Here, we present a salicylic acid (SA)-mediated binary association system (SAMBA), evolved from a tobacco SA receptor, that enables rapid protein–protein heterodimerization in response to SA or aspirin after hydrolysis. We demonstrate the broad applicability of SAMBA in various biological contexts, including SA-dependent reprogramming of a protein-based reaction–diffusion system, graded gating of calcium channels, inducible initiation of receptor tyrosine kinase-mediated signaling and gene expression, and tunable activation of chimeric antigen receptor T cells. Our work establishes SAMBA as a versatile chemogenetic platform that allows temporal control of biological processes and therapeutic cells both in vitro and in vivo.</p><p></p>

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Repurposing salicylic acid as a versatile inducer of proximity

  • 期刊论文

  • 发表日期：

    2025年6月13日

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  • Tianlu Wang,
  • Siyao Liu,
  • Yuepeng Ke,
  • Sher Ali,
  • Rui Wang,
  • Tingting Hong,
  • Ziying Liu,
  • Guolin Ma,
  • Tien-Hung Lan,
  • Fen Wang,
  • Michael X. Zhu,
  • Yun Huang,
  • Yubin Zhou

摘要

Chemically induced proximity (CIP) has remarkably advanced the development of molecular and cellular therapeutics. To maximize therapeutic potential, there is a pressing need to expand the repertoire of CIP systems of translational values, favoring chemical ligands that are cost-effective, structurally simple, biocompatible, reversible and have minimal side effects. Here, we present a salicylic acid (SA)-mediated binary association system (SAMBA), evolved from a tobacco SA receptor, that enables rapid protein–protein heterodimerization in response to SA or aspirin after hydrolysis. We demonstrate the broad applicability of SAMBA in various biological contexts, including SA-dependent reprogramming of a protein-based reaction–diffusion system, graded gating of calcium channels, inducible initiation of receptor tyrosine kinase-mediated signaling and gene expression, and tunable activation of chimeric antigen receptor T cells. Our work establishes SAMBA as a versatile chemogenetic platform that allows temporal control of biological processes and therapeutic cells both in vitro and in vivo.