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Customization and optimization of a histone h2a-based vector for targeted gene transfer to cancer cells
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Karjoo Diarkhan, Zahra. Customization and optimization of a histone h2a-based vector for targeted gene transfer to cancer cells. Retrieved from https://doi.org/doi:10.7282/T37S7QGT

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TitleCustomization and optimization of a histone h2a-based vector for targeted gene transfer to cancer cells
NameKarjoo Diarkhan, Zahra (author); Hatefi, Arash (chair); Minko, Tamara (internal member); You, Guofeng (internal member); GOW, ANDREW (outside member); Rutgers University; Graduate School - New Brunswick
Date Created2015
Other Date2015-01 (degree)
SubjectPharmaceutical Science, Gene therapy, Cancer--Treatment, Nanoparticles
Extent1 online resource (xii, 157 p. : ill.)
DescriptionDeveloping an efficient and safe system for gene delivery is considered the bottleneck of gene therapy, where a successful delivery of the nucleic acid can reverse a defective cellular pathway to normal, eradicate cancer at molecular level or simply make it more susceptible to current chemotherapies. Not only have the intracellular events played a crucial role for obtaining a successful gene delivery, but the interaction of nano-particles with extracellular factors should be studied as well. The goal of this study was to design, produce and optimize a non-viral gene delivery system for targeted delivery of nucleic acid such as reporter genes (e.g., green fluorescent protein) or therapeutic genes (e.g., suicide genes) to cancer cells. The system was designed in a way to be easily customized for different cancer types, still presenting a high level of targeted delivery. The first chapter of this thesis will focus on the concept of gene therapy and current systems used for this modality. Different types of vectors including viral and non-viral polymeric vectors will be discussed briefly and the advantages and disadvantages of each will be mentioned. We also discussed natured inspired biopolymers such as peptides and amino acid based vectors which are the fundamental premise of this study. In chapter II, the concept of suicide gene therapy will be explained. Additionally, the current enzyme/prodrug systems, different methods for delivery of suicide genes will be elaborated. In chapter III and IV, the new nanotechnology platform for targeted delivery of plasmid DNA to HER2-positive ovarian cancer cells and HER2-negative prostate cancer cells will be presented. In chapter III, the method for optimization of nanotechnology platform will be discussed and the features of optimized particles will be presented. Chapter IV explains the modification we introduced to the vectors’ primary structure to customize it for a different cell line. Also another method for optimization of amino-acid based vectors for in vivo delivery will be introduced. In these two chapters, the methods of designing and the efficiency of each vector to fulfill the expected goals as well as their safety will be discussed in details and supportive data will be presented.
NotePh.D.
NoteIncludes bibliographical references
Noteby Zahra Karjoo Diarkhan
Genretheses, ETD doctoral
Persistent URLhttps://doi.org/doi:10.7282/T37S7QGT
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.
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