Directed Evolution Enables Simultaneous Controlled Release of Multiple Therapeutic Proteins from Biopolymer-Based Hydrogels.

Autor: Teal CJ; Institute of Biomedical Engineering, 164 College Street, Toronto, ON, M5S 3G9, Canada.; Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON, M5S 3E1, Canada., Hettiaratchi MH; Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON, M5S 3E1, Canada.; Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, ON, M5S 3E5, Canada., Ho MT; Institute of Biomedical Engineering, 164 College Street, Toronto, ON, M5S 3G9, Canada.; Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON, M5S 3E1, Canada., Ortin-Martinez A; Donald K. Johnson Eye Institute, Krembil Research Institute, University Health Network, 399 Bathurst Street, Toronto, ON, M5T 2S8, Canada., Ganesh AN; Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON, M5S 3E1, Canada.; Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, ON, M5S 3E5, Canada., Pickering AJ; Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON, M5S 3E1, Canada.; Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, ON, M5S 3E5, Canada., Golinski AW; Department of Chemical Engineering and Materials Science, University of Minnesota-Twin Cities, 421 Washington Avenue Southeast, 356 Amundson Hall, Minneapolis, MN, 55455, USA., Hackel BJ; Department of Chemical Engineering and Materials Science, University of Minnesota-Twin Cities, 421 Washington Avenue Southeast, 356 Amundson Hall, Minneapolis, MN, 55455, USA., Wallace VA; Donald K. Johnson Eye Institute, Krembil Research Institute, University Health Network, 399 Bathurst Street, Toronto, ON, M5T 2S8, Canada.; Department of Laboratory Medicine and Pathobiology, University of Toronto, 27 King's College Circle, Toronto, ON, M5S 1A1, Canada.; Department of Ophthalmology and Vision Sciences, University of Toronto, 340 College Street, Toronto, ON, M5T 3A9, Canada., Shoichet MS; Institute of Biomedical Engineering, 164 College Street, Toronto, ON, M5S 3G9, Canada.; Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON, M5S 3E1, Canada.; Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, ON, M5S 3E5, Canada.; Department of Ophthalmology and Vision Sciences, University of Toronto, 340 College Street, Toronto, ON, M5T 3A9, Canada.; Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, ON, M5S 3H6, Canada.
Jazyk: angličtina
Zdroj: Advanced materials (Deerfield Beach, Fla.) [Adv Mater] 2022 Aug; Vol. 34 (34), pp. e2202612. Date of Electronic Publication: 2022 Jul 24.
DOI: 10.1002/adma.202202612
Abstrakt: With the advent of increasingly complex combination strategies of biologics, independent control over their delivery is the key to their efficacy; however, current approaches are hindered by the limited independent tunability of their release rates. To overcome these limitations, directed evolution is used to engineer highly specific, low affinity affibody binding partners to multiple therapeutic proteins to independently control protein release rates. As a proof-of-concept, specific affibody binding partners for two proteins with broad therapeutic utility: insulin-like growth factor-1 (IGF-1) and pigment epithelium-derived factor (PEDF) are identified. Protein-affibody binding interactions specific to these target proteins with equilibrium dissociation constants (K D ) between 10 -7 and 10 -8 m are discovered. The affibodies are covalently bound to the backbone of crosslinked hydrogels using click chemistry, enabling sustained, independent, and simultaneous release of bioactive IGF-1 and PEDF over 7 days. The system is tested with C57BL/6J mice in vivo, and the affibody-controlled release of IGF-1 results in sustained activity when compared to bolus IGF-1 delivery. This work demonstrates a new, broadly applicable approach to tune the release of therapeutic proteins simultaneously and independently and thus the way for precise control over the delivery of multicomponent therapies is paved.
(© 2022 Wiley-VCH GmbH.)
Databáze: MEDLINE
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