Engineering the NK1 Fragment of the Human Hepatocyte Growth Factor for Dual Use as a Potent Agonist and a Gene Therapy Delivery Vehicle
Abstract/Contents
- Abstract
- Regenerative medicine and wound healing are critically relevant topics in the current medical field. Estimates have placed the total number of patients impacted with chronic wounds in the US at 6.5 million, resulting in an annual expenditure of US$25 billion. Furthermore, the regenerative medicine industry has taken off, reaching over US$3 billion in both gross annual spending and sales. Growth factor-based therapies for use in regenerative medicine have shown initial promise in pre-clinical testing, but numerous obstacles to effective delivery and translation of expected activity have limited growth factors’ clinical potential. Accordingly, growth factor engineering techniques have been developed and employed to improve clinically relevant characteristics such as stability, circulation time, expression yield, and delivery methods. However, as is often the case in clinical applications, extremely potent therapeutics must be engineered to enable significant impact. This study integrates design and delivery methodologies from the fields of gene therapy and supercharged protein engineering to investigate the potential for the NK1 fragment of HGF to serve as a dual-use exogenous mitogen and plasmid delivery agent. Successful internalization was shown and characterized in mammalian cell systems. Additionally, rational engineering of covalent dimerization via the introduction of an N-terminal cysteine residue enhanced mitogenic activity in a number of NK1 variants. Finally, initial evidence is put forth for the ability of NK1 variants to complex with DNA, a critical step in preparing nonviral protein-based delivery vehicles for gene therapy applications.
Description
| Type of resource | text |
|---|---|
| Date created | May 11, 2016 |
Creators/Contributors
| Author | Mathy, Christopher |
|---|---|
| Primary advisor | Cochran, Jennifer |
| Advisor | Liphardt, Jan |
| Degree granting institution | Stanford University. Department of Bioengineering. |
Subjects
| Subject | NK1 |
|---|---|
| Subject | HGF |
| Subject | growth factor engineering |
| Subject | protein engineering |
| Subject | supercharged proteins |
| Subject | gene delivery |
| Subject | wound healing |
| Subject | regenerative medicine |
| Subject | bioengineering |
| Genre | Thesis |
Bibliographic information
Access conditions
- Use and reproduction
- User agrees that, where applicable, content will not be used to identify or to otherwise infringe the privacy or confidentiality rights of individuals. Content distributed via the Stanford Digital Repository may be subject to additional license and use restrictions applied by the depositor.
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
Preferred citation
- Preferred Citation
- Mathy, Christopher (2016). Engineering the NK1 Fragment of the Human Hepatocyte Growth Factor for Dual Use as a Potent Agonist and a Gene Therapy Delivery Vehicle. Stanford Digital Repository. Available at: http://purl.stanford.edu/kw533qg7356
Collection
Undergraduate Theses, School of Engineering
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- Contact
- cjmathy@gmail.com
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