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Lipid Modified Polymers for Transfection of Human CRL Fibroblasts, and for siRNA Mediated MDR Reversal in Melanoma Cancer Therapy

  • Author / Creator
    Abbasi Dezfouli, Meysam
  • Gene delivery for therapeutic purposes is quickly emerging as the best potential treatment option for inherited genetic diseases and cancer. Viral gene carriers have been the choice for this purpose due to their high efficiency, but harmful immunogenic and oncogenic host reactions have limited their in vivo use. Cationic polymers provide a safe alternative to viral carriers as they can be engineered to reduce immunogenic and toxic responses and serve therapeutic purposes in the body. Due to their strong positive charge, they are able to compact the negatively charged nucleotides to small nano-sized particles appropriate for cellular uptake. Additionally, they efficiently encapsulate the highly sensitive nucleotides, and protect them against degradation by the nucleases present at the physiological milieu. In this thesis work, I have used a novel approach for gene delivery by combining the critical properties of a cationic polymer (i.e., nucleotide condensing ability) with that of a fatty acid (i.e., lipid membrane compatibility). The resulting lipid modified polymer increased delivery of our gene of interest into target cells and resulted in increased siRNA delivery for cancer gene therapy.

  • Subjects / Keywords
  • Graduation date
    2010-11
  • Type of Item
    Thesis
  • Degree
    Doctor of Philosophy
  • DOI
    https://doi.org/10.7939/R3BD4M
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
    English
  • Institution
    University of Alberta
  • Degree level
    Doctoral
  • Department
    • Department of Biomedical Engineering
  • Supervisor / co-supervisor and their department(s)
    • Uludag, Hasan (Chemical & Materials Engineering)
  • Examining committee members and their departments
    • Weinfeld, Michael (Oncology)
    • Willman, Alan (Biomedical Engineering)
    • Hugh, Judith (Laboratory Medicine & Pathology)
    • Burrell, Robert (Biomedical Engineering)
    • Pun, Suzie (Bioengineering)
    • Berthiaume, Luc (Cell Biology)