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Updated: Mar 24, 2026

Direct Protein Delivery to Mammalian Cells Using Cell-permeable Cys2-His2 Zinc-finger Domains
Published on: March 25, 2015
Designer protein delivery: From natural to engineered affinity-controlled release systems
Malgosia M Pakulska1, Shane Miersch2, Molly S Shoichet3
1Department of Chemical Engineering and Applied Chemistry, Institute of Biomaterials and Biomedical Engineering, and Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.
Affinity-controlled release uses molecular binding to control therapeutic protein delivery, offering an alternative to degradation-based methods. Advances in protein, peptide, and aptamer design enhance this controlled release strategy.
Area of Science:
- Biochemistry
- Biotechnology
- Drug Delivery
Background:
- Exploiting molecular binding affinities is common in diagnostics and drug development.
- Controlling biomolecule release using these affinities is an emerging strategy.
- Affinity-controlled release leverages reversible noncovalent interactions for sustained protein delivery.
Purpose of the Study:
- To review advances in discovering or designing binding partners for affinity-controlled release.
- To highlight methods for controlling therapeutic protein release from a vehicle.
Main Methods:
- In vitro selection of proteins, peptides, and oligonucleotides (aptamers).
- Directed evolution techniques for optimizing binding partners.
- Computational design approaches to aid in partner discovery.
Main Results:
- Demonstrates the potential of affinity-controlled release as a novel drug delivery system.
- Highlights the role of binding affinity, kinetics, and partner concentration in release modulation.
- Reviews various methods for generating and refining binding partners.
Conclusions:
- Affinity-controlled release offers a distinct mechanism for sustained drug delivery compared to degradation-based systems.
- Advances in molecular selection, evolution, and computational design are crucial for developing effective binding partners.
- This strategy holds promise for future therapeutic protein formulations.
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