Genetic control of T cell proliferation with synthetic RNA devices
Abstract/Contents
- Abstract
- The tools of synthetic biology offer the potential to design, construct, and reprogram natural biological systems. Programmed cells can interface with existing biological networks and introduce novel functionality that is otherwise difficult to reproduce from nature. Recent advances in the field have led to growing interest in constructing complex genetic systems in mammalian cells for various applications in health and medicine. One area that has gained significant interest is in cell-based therapy, where cells are used as therapeutic agents to treat diseases. In particular, the application of engineered autologous T cells for adoptive immunotherapy of cancer is currently under intensive translational research. This treatment modality has demonstrated remarkable success in clinical trials, but efficacy has been hampered by severe toxicities that were difficult to anticipate. Here, we present the development of RNA-based regulatory systems that can control T cell proliferation in response to a small molecule drug input. The RNA devices engineered in this work respond to (6R)-folinic acid, a pharmaceutical drug that is readily available and safe for prolonged administration in clinical settings. Through rational design and structural engineering, we constructed drug-responsive ribozyme- and miRNA-based devices to regulate the expression of transgenes and endogenous genes, respectively. To explore the possibility of implementing multiple layers of control, we further integrated the individual control systems into a single platform to exert stringent control over T cell proliferation. The RNA regulatory devices are also versatile and may be adapted more broadly for other therapeutic applications that require transgene or endogenous gene control.
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 | Wong, Remus S |
|---|---|
| Associated with | Stanford University, Department of Bioengineering. |
| Primary advisor | Smolke, Christina D |
| Thesis advisor | Smolke, Christina D |
| Thesis advisor | Calos, Michele P |
| Thesis advisor | Lewis, David |
| Advisor | Calos, Michele P |
| Advisor | Lewis, David |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Remus S. Wong. |
|---|---|
| Note | Submitted to the Department of Bioengineering. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2016. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2016 by Remus S Wong
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