Development Of Novel Exosome-Based Delivery System For Proteins
| dc.contributor.author | Chew, Yik Wei | |
| dc.date.accessioned | 2017-01-24T03:49:49Z | |
| dc.date.available | 2017-01-24T03:49:49Z | |
| dc.date.issued | 2016-03 | |
| dc.description.abstract | A cell contains thousands of proteins that contribute to critical signalling pathways in normal cellular functions. Most diseases somehow result from the malfunction of one or more of such proteins. To palliate such dysfunction, protein therapy that makes use of therapeutic proteins to correct the cellular functions is considered the most direct and safe approach for treating diseases. There are more than 1,500 potential disease treatment targets that reside inside the cell, without a clear receptor pathway for their specific targeting. The need for intracellular delivery and targeting select host cell compartment represents a formidable hurdle to the development of novel prospective intracellular targeting protein-based biologics. Exosomes, 40-120 nm membrane vesicles secreted by cells, have recently emerged as promising natural vehicles for the delivery of macromolecules. Exosomes interact with cells and affect the functions of neighbouring cells through intercellular transfer of mRNA, microRNA, receptors and enzymes, and found to play important roles in immune dysregulation. A number of viral proteins such as HIV-1 Nef, Vif and VSV-G protein are reported to induce exosome production. These observations lead us to hypothesize that simultaneous overexpression of exosome inducing proteins (ExIP) and a heterologous protein from the same plasmid vector will result in the production of exosomes that contain the desired protein. To test our hypothesis we have constructed bicistronic mammalian expression vectors that concomitantly express various ExIPs and GFP as a reporter protein. We have found that both HIV-1 Nef and VSV-G proteins induce the induction of GFP-containing exosomes. These observations may lead to novel possibilities for the efficient delivery of recombinant proteins (such as antibodies) and opens up new avenues in terms of the development of intracellular protein biologic drugs. | en_US |
| dc.identifier.uri | http://hdl.handle.net/123456789/3552 | |
| dc.language.iso | en | en_US |
| dc.publisher | Universiti Sains Malaysia | en_US |
| dc.subject | Exosomes | en_US |
| dc.title | Development Of Novel Exosome-Based Delivery System For Proteins | en_US |
| dc.type | Thesis | en_US |
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