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GENOMIC STABILITY OF TRANSCRIPTIONALLY TARGETED REPLICATION COMPETENT RETROVIRAL VECTORS
by
Laurent Yoon
________________________________________________________________________
A Dissertation Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirement for the Degree
DOCTOR OF PHILOSOPHY
(BIOCHEMISTRY AND MOLECULAR BIOLOGY)
May 2008
Copyright 2008 Laurent Yoon
Object Description
| Title | Genomic stability of transcriptionally targeted replication competent retroviral vectors |
| Author | Yoon, Laurent |
| Author email | ltyoon@gmail.com |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Biochemistry & Molecular Biology |
| School | Keck School of Medicine |
| Date defended/completed | 2005-04-20 |
| Date submitted | 2008 |
| Restricted until | Restricted until 21 Apr. 2010. |
| Date published | 2010-04-21 |
| Advisor (committee chair) | Cannon, Paula |
| Advisor (committee member) |
Kasahara, Noriyuki Kohn, Donald |
| Abstract | Advances in techniques for gene transfer and expression have made feasible the treatment of malignancies at the genetic level by introduction of exogenous genes into tumor cells. Numerous clinical trials of cancer gene therapy have been initiated utilizing replication defective vectors only to face limited success due to low, often undetectable, level of transduction efficiency. Replication competent vectors have been developed more recently demonstrating efficient transduction as well as tissue specific expression. These studies demonstrate the potential benefits of utilizing replication competent retrovirus as efficient gene delivery vehicles but undermine the potential risks in their innate tendency to mutate potentially resulting in an uncontrolled spread of replication-competent mutant virus with adverse effects on normal cells. To understand the potential risks in persistent long-term infection of replication competent retrovirus vectors (RCR), our study focused on the genomic stability of the long terminal repeat (LTR) of murine leukemia virus (MLV) responsible for driving the expression of viral genes for replication since our vector designs to date manipulate this region to drive selective replication of vectors. After long term propagation of various RCR vectors in various tumor cell lines, we demonstrate here that there are regions of instability in the LTR but very low risk in having a mutant virus with adverse effects as the very reason for utilizing RCR vector is for efficient spread and the vectors are normally equipped with a self-destruction mechanism. |
| Keyword | gene therapy; replication competent retrovirus; genomic stability |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Type | texts |
| Legacy record ID | usctheses-m1164 |
| Rights | Yoon, Laurent |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | http://www.usc.edu/isd/libraries/services/ask_a_librarian/email/ |
| Filename | etd-Yoon-20080421 |
| Archival file | uscthesesreloadpub_Volume26/etd-Yoon-20080421.pdf |
Description
| Title | Page 1 |
| Full text | GENOMIC STABILITY OF TRANSCRIPTIONALLY TARGETED REPLICATION COMPETENT RETROVIRAL VECTORS by Laurent Yoon ________________________________________________________________________ A Dissertation Presented to the FACULTY OF THE GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirement for the Degree DOCTOR OF PHILOSOPHY (BIOCHEMISTRY AND MOLECULAR BIOLOGY) May 2008 Copyright 2008 Laurent Yoon |
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