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Related Experiment Video

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Orthogonal Tri-Modular Coiled-Coil Assembly for Programmable Multi-Cargo Display on Escherichia coli Nissle 1917.

Yong Joon Cho1, Gyu-Jin Lee1, Jong-Ha Park1

  • 1Department of Chemical Engineering, Pukyong National University, Busan, Republic of Korea.

Small (Weinheim an Der Bergstrasse, Germany)
|March 20, 2026
PubMed
Summary
This summary is machine-generated.

Researchers developed Tri-specific Scaffold Cells (TriSCs), a novel living medicine platform. This biointerface enables dynamic, reversible assembly of therapeutic payloads for advanced precision theranostics.

Keywords:
coiled‐coil interactionslive biotherapeutic productsmultiplex surface displayorthogonal assemblyprogrammable living scaffold

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Area of Science:

  • Biotechnology
  • Synthetic Biology
  • Microbial Engineering

Background:

  • Live biotherapeutic products (LBPs) offer targeted therapeutic interventions but face limitations in surface functionalization, hindering multiplexing and dynamic payload assembly.
  • Current methods like genetic fusion or covalent modification are static, restricting the adaptability and programmability of LBPs.
  • There is a need for a versatile living scaffold that allows for controlled, reversible, and multiplexed display of functional modules.

Purpose of the Study:

  • To engineer a novel tri-modular, orthogonally programmable living scaffold (TriSCs) based on Escherichia coli Nissle 1917.
  • To develop a "mix-and-go" strategy for spontaneous, specific, and reversible assembly of payloads on the bacterial outer membrane.
  • To demonstrate the potential of TriSCs for enhanced therapeutic efficacy and real-time bioimaging in theranostics.

Main Methods:

  • Engineered Escherichia coli Nissle 1917 to display three distinct α-helical motifs on the outer membrane, forming TriSCs.
  • Utilized coiled-coil interactions for orthogonal, reversible, and spontaneous assembly of functional modules (nanobodies, fluorescent reporters).
  • Assessed the anticancer activity of co-displayed nanobodies and evaluated the utility of a fluorescent reporter for bioimaging.

Main Results:

  • Successfully created a reconfigurable biointerface on TriSCs enabling dynamic payload assembly.
  • Demonstrated simultaneous and selective recruitment of multiple functional modules without structural interference.
  • Achieved enhanced anticancer activity through spatial co-display of DR5 agonistic and EGFR-targeting nanobodies compared to soluble combinations.
  • Validated real-time bioimaging capability via modular incorporation of a fluorescent reporter.

Conclusions:

  • TriSCs provide a dynamic and programmable platform for LBPs, integrating orthogonality, reversibility, and multiplexing.
  • The "mix-and-go" assembly strategy overcomes limitations of static functionalization, enabling versatile payload configuration.
  • TriSCs hold significant promise for precision theranostics and the development of next-generation bioengineered therapeutics.