Restoration of miR-185 in combination with BCR-ABL downregulation by non-viral delivery of siRNA with lipomeric carriers and lipid nanoparticles sensitizes drug resistant cells to TKIs

Over 130,000 people in Canada are living with and are actively being treated for bloodod cancers. The main problem with our available current therapy is their inability to kill blood cancer stem cells that are responsible for drug resistance and cancer relapse. Our lab has found that targeting a novel pathway using gene therapy to restore the activity of miR-185 can significantly impair the growth of blood cancer stem cells and sensitize them to therapy. This study will investigate the combination of targeting several key proteins using miR-185 and targeting BCR-ABL using siRNA in order to effectively eradicate blood cancer stem cells. Importantly this treatment strategy does not show any side effects in normal blood stem cells, providing a therapeutic window to specifically target blood cancer stem cells. This study aims to investigate the therapeutic potential of this gene combination using gold-standard lipid nanoparticle technology and a newly established animal cancer model. We hope this work will provide a proof-of-concept for more effective strategies to overcome drug resistance and improve the outcomes of patients diagnosed with blood cancers.