Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Microbiology and Immunology

Supervisor

Dr. James Koropatnick

Abstract

RNAi (RNA interference) is emerging as a promising tool for cancer therapy. Small interfering RNA (siRNA) molecules are activated in that pathway to reduce specific tumour cell RNAs that mediate malignancy. SiRNA treatment has been primarily limited to in vitro studies: lack of efficient, preferential in vivo delivery to target cells remains a major obstacle. Many human tumours overexpress folate receptors (FR), and siRNA-mediated reduction of thymidylate synthase (TS) sensitizes tumour cells to anti-TS drugs. I developed a folate-containing cationic liposome to preferentially deliver anti-TS siRNA to FR-expressing human tumour cells. I show, in vitro, that liposome-encapsulated siRNA (but not free siRNA) is delivered to human tumour cells, and that FR-targeting liposomes preferentially deliver siRNA into FR-positive human tumour cells. However, liposome-delivered siRNA did not reduce TS mRNA, an obstacle that must be overcome before the advantage of preferential siRNA delivery can be realized in vivo.


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