Enzyme-instructed siRNA Release and Functional Self-assembly of Peptide-based Delivery System
| dc.contributor.author | Jiao, Yuxiao | |
| dc.date.accessioned | 2021-08-27T15:38:20Z | |
| dc.date.available | 2021-08-27T15:38:20Z | |
| dc.date.issued | 2021-08-27 | |
| dc.date.submitted | 2021-08-23 | |
| dc.description.abstract | Cell-penetrating peptide (CPP)-based small interfering RNA (siRNA) delivery is one of the approaches with great potential to achieve RNA interference (RNAi) applied in gene therapy. CPP-based siRNA carriers hold many merits, including biodegradability, high transmembrane efficiency, and capability of endosomal escape. Despite considerably high transfection efficiency achieved, there are still many challenges in further improving the CPP-based siRNA delivery systems. This proposal focuses on two of the challenges: (1) the dissociation of negatively charged siRNA from a positively charged peptide; and (2) minimization of cytotoxicity of CPPs while maintaining capacity in endosomal escape. Herein, we propose to utilize enzyme-catalyzed phosphorylation to induce the transfer of negatively charged phosphate groups onto the cationic CPPs formulated with siRNA; the emergent phosphate groups can facilitate the dissociation of siRNAs from the complex due to electrostatic repulsion between the two negatively charged species, the phosphate groups on the peptide and the siRNA. The presence of phosphate groups also alters the balance between repulsive and attractive forces that govern the self-assembly of the peptide, resulting in conformational changes. | en |
| dc.identifier.uri | http://hdl.handle.net/10012/17285 | |
| dc.language.iso | en | en |
| dc.pending | false | |
| dc.publisher | University of Waterloo | en |
| dc.title | Enzyme-instructed siRNA Release and Functional Self-assembly of Peptide-based Delivery System | en |
| dc.type | Master Thesis | en |
| uws-etd.degree | Master of Applied Science | en |
| uws-etd.degree.department | Chemical Engineering | en |
| uws-etd.degree.discipline | Chemical Engineering | en |
| uws-etd.degree.grantor | University of Waterloo | en |
| uws-etd.embargo.terms | 0 | en |
| uws.contributor.advisor | Chen, Pu | |
| uws.contributor.affiliation1 | Faculty of Engineering | en |
| uws.peerReviewStatus | Unreviewed | en |
| uws.published.city | Waterloo | en |
| uws.published.country | Canada | en |
| uws.published.province | Ontario | en |
| uws.scholarLevel | Graduate | en |
| uws.typeOfResource | Text | en |