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Reprogramming chemically induced dimerization systems with genetically encoded nanobodies.

Tianlu Wang1, Tatsuki Nonomura1, Mingguang Cui1

  • 1Centre for Translational Cancer Research, Institute of Biosciences and Technology, Texas A&M University Houston TX 77030 USA lhetamu@gmail.com yubinzhou@tamu.edu.

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Summary
This summary is machine-generated.

This study repurposed existing chemically induced proximity (CIP) systems using nanobodies. Researchers modified the COSMO and rapamycin systems to enable caffeine-inducible heterodimerization and rapamycin-dependent OFF-switching, expanding CIP toolkit capabilities.

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Synthetic Biology

Background:

  • Chemically induced proximity (CIP) systems utilize small molecules to control protein-protein interactions for therapeutic applications.
  • Repurposing existing CIP systems is a cost-effective strategy to develop novel functionalities.
  • Genetically encoded nanobodies can overcome limitations in specific biological contexts.

Purpose of the Study:

  • To reprogram established CIP systems using nanobodies.
  • To confer novel functions onto existing chemogenetic tools.
  • To expand the repertoire of available CIP technologies.

Main Methods:

  • Incorporation of the bivalent COSMO module and UniRapR into an anti-mCherry nanobody.
  • Engineering of a caffeine-inducible heterodimerization system from a homodimeric COSMO system.
  • Transformation of a rapamycin-dependent ON switch into an OFF switch.

Main Results:

  • Successfully reprogrammed the COSMO system into a caffeine-inducible heterodimerization system.
  • Successfully transformed the rapamycin-dependent system into an OFF switch.
  • Demonstrated novel functionality of existing chemogenetic tools through nanobody engineering.

Conclusions:

  • Genetically encoded nanobodies can effectively repurpose existing CIP systems.
  • This approach expands the versatility and applicability of chemogenetic toolkits.
  • The engineered systems offer new possibilities for smart and personalized therapies.