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Stem cell-based ovarian cancer suicide gene therapy
Descriptive
TitleInfo
Title
Stem cell-based ovarian cancer suicide gene therapy
Name
(type = personal)
NamePart
(type = family)
Salman Noori
NamePart
(type = given)
Faranak
NamePart
(type = date)
1986-
DisplayForm
Faranak Salman Noori
Role
RoleTerm
(authority = RULIB)
author
Name
(type = personal)
NamePart
(type = family)
Minko
NamePart
(type = given)
Tamara
DisplayForm
Tamara Minko
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
chair
Name
(type = corporate)
NamePart
Rutgers University
Role
RoleTerm
(authority = RULIB)
degree grantor
Name
(type = corporate)
NamePart
Graduate School - New Brunswick
Role
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(authority = RULIB)
school
TypeOfResource
Text
Genre
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theses
OriginInfo
DateCreated
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(qualifier = exact)
2015
DateOther
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(type = degree)
2015-10
CopyrightDate
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(qualifier = exact)
2015
Place
PlaceTerm
(type = code)
xx
Language
LanguageTerm
(authority = ISO639-2b);
(type = code)
eng
Abstract
(type = abstract)
Cancer 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.
Subject
(authority = RUETD)
Topic
Pharmaceutical Science
RelatedItem
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TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier
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ETD
Identifier
ETD_6789
PhysicalDescription
Form
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electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
1 online resource (xi, 142 p. : ill.)
Note
(type = degree)
Ph.D.
Note
(type = bibliography)
Includes bibliographical references
Subject
(authority = ETD-LCSH)
Topic
Cancer--Gene therapy
Subject
(authority = ETD-LCSH)
Topic
Ovaries--Cancer
Subject
(authority = ETD-LCSH)
Topic
Stem cells
Note
(type = statement of responsibility)
by Faranak Salman Noori
RelatedItem
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TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier
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rucore19991600001
Location
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NjNbRU
Identifier
(type = doi)
doi:10.7282/T38W3G9H
Genre
(authority = ExL-Esploro)
ETD doctoral
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Rights
RightsDeclaration
(ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder
(type = personal)
Name
FamilyName
Salman Noori
GivenName
Faranak
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime
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(qualifier = exact);
(point = start)
2015-09-25 14:40:16
AssociatedEntity
Name
Faranak Salman Noori
Role
Copyright holder
Affiliation
Rutgers University. Graduate School - New Brunswick
AssociatedObject
Type
License
Name
Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
RightsEvent
DateTime
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(qualifier = exact);
(point = start)
2015-10-31
DateTime
(encoding = w3cdtf);
(qualifier = exact);
(point = end)
2017-10-30
Type
Embargo
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after October 30th, 2017.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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Technical
RULTechMD
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ContentModel
ETD
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windows xp
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