2017 March 23: BME PhD Dissertation "siRNA Delivery with Lipopolymers in Chronic Myeloid Leukemia"

Thursday March 23, 2017 10:00AM - 11:00AM @ 1-075 Research Transition Facility, Juliana Valencia, PhD Candidate

Juliana Valencia, PhD Candidate, Biomedical Engineering, University of Alberta - 22 March 2017

Date: Thursday, March 23, 2017
Time:
10:00AM - 11:00AM
Location:
1-075 Research Transition Facility

Abstract:


Chronic Myeloid Leukemia (CML) arises from the acquisition of BCR-ABL oncogene in normal hematopoietic stem cells that progressively outgrow the normal hematopoietic stem cells in the stem cell niche and subsequently leads to an uncontrolled expansion of immature myeloid cells. Tyrosine kinase inhibitors (TKIs) used to target the ABL tyrosine kinase have shown significantly increased clinical outcomes in CML patients, however, patients in blast crisis phase are more likely to relapse and develop resistance often due to mutations in the TKI domain and innate or acquired insensitivity of CML stem cells. RNAi represents a promising alternative for the treatment of CML as small interference RNA (siRNA) molecules can be applied to the silencing of specific targets that modulate the biological outcome and induce therapeutic effects. However, potent carriers that can overcome delivery barriers of RNAi agents and are effective in difficult-to-transfect cells -such as CML cells- are needed for the progression of siRNA-based therapies towards clinical applications. In this thesis work, I explore the use of lipid-modified polyethylenimines (PEI) in in vitro and in vivo CML models and evaluate their siRNA transfection efficiency in terms of cytotoxicity, siRNA uptake, internalization, gene silencing and biological effects. The results from this study revealed the potential of siRNA-based drugs and are encouraging for the future design of non-viral delivery system with clinical translation capabilities for the treatment of CML and other leukemias.