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Directed Evolution Enables Simultaneous Controlled Release of Multiple Therapeutic Proteins from Biopolymer-Based
Carter J Teal1,2, Marian H Hettiaratchi2,3, Margaret T Ho1,2
1Institute of Biomedical Engineering, 164 College Street, Toronto, ON, M5S 3G9, Canada.
Advanced Materials (Deerfield Beach, Fla.)
|July 5, 2022
Summary
Researchers engineered affibody binding partners to control the release of therapeutic proteins, enabling independent and sustained delivery of insulin-like growth factor-1 (IGF-1) and pigment epithelium-derived factor (PEDF) over seven days.
Area of Science:
- Biotechnology
- Protein Engineering
- Drug Delivery Systems
Background:
- Current biologic combination therapies lack independent control over drug release rates, limiting efficacy.
- Developing tunable release mechanisms is crucial for advanced combination therapies.
Purpose of the Study:
- To engineer affibody binding partners for independent control of therapeutic protein release.
- To demonstrate sustained and simultaneous release of insulin-like growth factor-1 (IGF-1) and pigment epithelium-derived factor (PEDF).
Main Methods:
- Directed evolution was employed to create low-affinity affibody binding partners for specific therapeutic proteins.
- Affibodies were conjugated to hydrogels via click chemistry for controlled release.
- The system's efficacy was validated using in vivo studies with C57BL/6J mice.
Main Results:
- Specific affibody binding partners for IGF-1 and PEDF were identified with dissociation constants (KD) in the 10-7 to 10-8 m range.
- Sustained, independent, and simultaneous release of bioactive IGF-1 and PEDF was achieved over 7 days.
- In vivo studies showed sustained activity of IGF-1 following affibody-controlled release compared to bolus delivery.
Conclusions:
- A novel, broadly applicable method for independently tuning therapeutic protein release was developed.
- This approach enables precise control over the delivery of multicomponent therapies.
- The engineered affibody system offers a promising strategy for advanced drug delivery applications.
