The use of ultrasound to facilitate the delivery of genetic-based therapeutic strategies
Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2004.
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| Format: | Thesis |
| Language: | en_US |
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Massachusetts Institute of Technology
2005
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| Online Access: | http://hdl.handle.net/1721.1/28735 |
| _version_ | 1826188765947756544 |
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| author | Silcox, Christina, 1978- |
| author2 | Kullervo Hynynen. |
| author_facet | Kullervo Hynynen. Silcox, Christina, 1978- |
| author_sort | Silcox, Christina, 1978- |
| collection | MIT |
| description | Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2004. |
| first_indexed | 2024-09-23T08:04:42Z |
| format | Thesis |
| id | mit-1721.1/28735 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T08:04:42Z |
| publishDate | 2005 |
| publisher | Massachusetts Institute of Technology |
| record_format | dspace |
| spelling | mit-1721.1/287352019-04-09T16:32:13Z The use of ultrasound to facilitate the delivery of genetic-based therapeutic strategies Silcox, Christina, 1978- Kullervo Hynynen. Massachusetts Institute of Technology. Dept. of Electrical Engineering and Computer Science. Massachusetts Institute of Technology. Dept. of Electrical Engineering and Computer Science. Electrical Engineering and Computer Science. Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2004. Includes bibliographical references (leaves 53-62). (cont.) preliminary experiments will eventually lead to a clinical methodology where ultrasound-enhanced gene therapy transfection would be followed with ultrasound-directed spatial control of gene expression. Gene therapy is the introduction of exogenous genes to a cell to "fool" the cell into producing the coding protein. There are ongoing studies in cancer-killing gene therapies, kidney cell regeneration and many genetic disorders such as cystic fibrosis and severe combined immunodeficiency (SCID). However, it has been discovered that developing the therapy is not enough. A method to deliver the drugs is equally important. The objective of this work was to explore two potential uses of ultrasound for gene delivery. The first is to determine if ultrasound-induced cavitation can be used to enhance in vivo transfection of gene therapy. Second, to use non-invasive ultrasonic heating to spatially control gene therapy expression in vivo after delivery. In the first phase of this project, feasibility experiments were performed to show an increase in transfection efficiency occurred when using microbubbles, ultrasound, plasmid and genes compared to plasmid and genes alone. An ultrasound transducer was then designed to optimize experimental conditions for invasive in vivo experiments taking into consideration optimal transducer size, focal distance, and frequency. When testing the transducer, a potential side effect to using ultrasound to increase transfection was discovered. In the second phase of exploration, the use of MRI-monitored ultrasound to induce enhanced expression of luciferase after local injection of the gene construct Ad-HSP-Luc was explored. Using a construct that includes an hsp promoter allows the activation of the associated transgene only in areas that are subsequently heated after injection. Increased luciferase expression was observed in areas that were exposed to ultrasonic heating. It is hoped that the positive results of these by Christina Silcox. S.M. 2005-09-27T18:03:09Z 2005-09-27T18:03:09Z 2004 2004 Thesis http://hdl.handle.net/1721.1/28735 59668840 en_US M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission. http://dspace.mit.edu/handle/1721.1/7582 62 leaves 3471505 bytes 3477274 bytes application/pdf application/pdf application/pdf Massachusetts Institute of Technology |
| spellingShingle | Electrical Engineering and Computer Science. Silcox, Christina, 1978- The use of ultrasound to facilitate the delivery of genetic-based therapeutic strategies |
| title | The use of ultrasound to facilitate the delivery of genetic-based therapeutic strategies |
| title_full | The use of ultrasound to facilitate the delivery of genetic-based therapeutic strategies |
| title_fullStr | The use of ultrasound to facilitate the delivery of genetic-based therapeutic strategies |
| title_full_unstemmed | The use of ultrasound to facilitate the delivery of genetic-based therapeutic strategies |
| title_short | The use of ultrasound to facilitate the delivery of genetic-based therapeutic strategies |
| title_sort | use of ultrasound to facilitate the delivery of genetic based therapeutic strategies |
| topic | Electrical Engineering and Computer Science. |
| url | http://hdl.handle.net/1721.1/28735 |
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