Engineering bivalency and bispecificity in protein therapeutics and protein scaffold development
Abstract/Contents
- Abstract
- Multivalent and multifunctional proteins are abundant in nature. The avidity effect, a core principle of multivalent molecules, allows these proteins to tune biological functions and responses across a large dynamic range with varying specificity. Many protein therapeutics also take advantage of this evolvable tunability, the canonical example being the antibody. This thesis consists of two separate sections. Section One: I focus on the avidity effect of multivalent proteins and its therapeutic uses. As an illustrative case, our lab had previously created a protein variant that monomerically binds the c-MET tyrosine kinase. By dimerizing this variant, we find that we greatly increase its efficacy through increased apparent affinity to cell surface c-MET. Section Two: I focus on multispecific proteins and their uses in medical applications. Most current therapeutic protein scaffolds are single protein domains with monomeric binding and function. Combining these scaffolds to create multispecific functionality presents manufacturing challenges. Here the vascular endothelial growth factor (VEGF) protein is used as a stable, naturally bivalent scaffold for engineering bispecific proteins.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2016 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Liu, Cassie J |
|---|---|
| Associated with | Stanford University, Department of Chemical Engineering. |
| Primary advisor | Cochran, Jennifer R |
| Primary advisor | Dunn, Alexander Robert |
| Thesis advisor | Cochran, Jennifer R |
| Thesis advisor | Dunn, Alexander Robert |
| Thesis advisor | Khosla, Chaitan, 1964- |
| Advisor | Khosla, Chaitan, 1964- |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Cassie J. Liu. |
|---|---|
| Note | Submitted to the Department of Chemical Engineering. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2016. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2016 by Cassie Jen-I Liu
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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