Home
Resource
Stem cell-based ovarian cancer suicide gene therapy
PDF
PDF format is widely accepted and good for printing.
Plug-in required
PDF-1(2.70 MB)
Citation & Export
View Usage Statistics
Staff View

Citation & Export
Hide

Simple citation

Salman Noori, Faranak. Stem cell-based ovarian cancer suicide gene therapy. Retrieved from https://doi.org/doi:10.7282/T38W3G9H

Export

Click here for information about Citation Management Tools at Rutgers.

Statistics
Hide

Description

TitleStem cell-based ovarian cancer suicide gene therapy
NameSalman Noori, Faranak (author); Minko, Tamara (chair); Rutgers University; Graduate School - New Brunswick
Date Created2015
Other Date2015-10 (degree)
SubjectPharmaceutical Science, Cancer--Gene therapy, Ovaries--Cancer, Stem cells
Extent1 online resource (xi, 142 p. : ill.)
DescriptionCancer is a leading cause of death worldwide, resulting in 8.2 million deaths in 2012. Tumor suicide gene therapy is among the novel targeted therapeutics that has demonstrated promising results. There are two important factors that specify the efficiency and safety of the suicide gene therapy systems. One is vector safety and efficiency and the other enzyme/prodrug anticancer efficacy. Among the vectors employed for delivery of therapeutics, mesenchymal stem cells (MSCs) have attracted tremendous amount of attention due to their unique features such as inherent tumor tropism and low immunogenicity. The objective of this research was to take advantage of MSCs as cell-based vectors to develop an efficient and safe suicide gene therapy system for cancer. As a first step towards achieving the objective, I engineered a panel of MSCs that were genetically modified to express five different suicide genes and compared their anti-tumor efficiency in vitro and in vivo. Among the enzyme/prodrug systems tested, genetically modified MSCs that expressed yeast cytosine deaminase enzyme (yCD-UPRT) in combination with prodrug 5-fluorocytosine (5FC) demonstrated the highest anti-tumor efficacy. In the next step we focused on developing a safe and efficient method for stem cell engineering. Since current commercially available transfection agents are inefficient and toxic to MSCs, I made an attempt to develop a safe and efficient gene delivery system suitable for MSC engineering. Using a previously developed vector in Dr. Hatefi’s lab as a template, I recombinantly engineered a new vector for MSC transfection. This vector is comprised of a cell penetrating peptide for penetration into MSCs, four histone H2A repeats to condense plasmid DNA (pDNA) into nanosize particles and a fusogenic peptide named GALA to facilitate endosomal escape. The results of this study illustrated that the newly developed recombinant vector could efficiently and safely transfect MSCs. In conclusion we not only successfully developed a safe and efficient method for stem cell engineering but also identified an enzyme/prodrug system that could be used for effective treatment of ovarian cancer.
NotePh.D.
NoteIncludes bibliographical references
Noteby Faranak Salman Noori
Genretheses, ETD doctoral
Persistent URLhttps://doi.org/doi:10.7282/T38W3G9H
Languageeng
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.
Version 8.5.5
Rutgers University Libraries - Copyright ©2024