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Programmable macromolecule delivery via engineered trogocytosis.

Xinyi Chen1, Yinglin Situ1, Yuexuan Yang1

  • 1Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.

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Researchers developed a novel cell-based delivery system using trogocytosis to transfer proteins and functional cargos between cells. This programmable framework enables precise macromolecular delivery for applications like genome editing and cell ablation.

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Area of Science:

  • Cell Biology
  • Biotechnology
  • Molecular Medicine

Background:

  • Trogocytosis, the transfer of membrane fragments during cell contact, shows promise for macromolecular delivery.
  • Existing limitations include uncertain cargo fate, cargo type constraints, and limited generalizability.

Purpose of the Study:

  • To engineer cells for enhanced protein transfer via trogocytosis.
  • To develop a programmable, logic-gate-controlled system for targeted macromolecular delivery.

Main Methods:

  • Engineered donor cells with designed receptors for specific ligand recognition.
  • Incorporated pH-responsive membrane fusion and inducible cargo localization/release.
  • Integrated logic gate-based control for sensing multiple inputs.

Main Results:

  • Demonstrated successful protein transfer from engineered donor to recipient cells.
  • Identified key principles for optimizing contact-mediated transfer and functionalization.
  • Developed the TRANSFER system for versatile cargo delivery across cell types.

Conclusions:

  • Trogocytosis can be programmed for efficient, cell-based macromolecular delivery.
  • The TRANSFER system offers a novel framework for applications in genome editing and targeted cell ablation.