title: Progress in RNAi-mediated Molecular Therapy of Acute and Chronic Myeloid Leukemia.
abstract: Leukemias arise from genetic alterations in normal hematopoietic stem or progenitor cells, leading to impaired regulation of proliferation, differentiation, apoptosis, and survival of the transformed cells. With the advent of RNA interference (RNAi) and the short interfering RNA (siRNA) as its pharmacological mediator, it is becoming possible to modulate specific targets at will. This article summarizes current attempts to utilize RNAi reagents for therapy of leukemias, focusing on acute and chronic myeloid leukemia. We first present unique aspects of RNAi-mediated therapy, followed by a brief background on the delivery technology of RNAi reagents. The need for leukemia-specific delivery of siRNA is discussed by describing approaches that targeted agents to leukemic cells. Pharmacokinetics and biodistribution of RNAi agents are then presented, highlighting the critical issues pertinent to emerging siRNA therapy. Efforts to deliver specific RNAi therapies are then summarized in the context of expected clinical outcomes, focusing on limiting leukemic cell survival, sensitizing malignant cells to chemotherapy, mobilization of leukemic cells, and eradication of leukemic stem cells. We conclude with a perspective on the future of RNAi therapy, emphasizing the technological requirements and mechanistic challenges for clinical entry.
authors.affiliation: Department of Chemical & Materials Engineering, Faculty of Engineering, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Breanne
authors.initials: B
authors.lastname: Landry
authors.affiliation: Department of Biomedical Engineering, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Juliana
authors.initials: J
authors.lastname: Valencia-Serna
authors.affiliation: Department of Biomedical Engineering, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Hilal
authors.initials: H
authors.lastname: Gul-Uludag
authors.affiliation: 1] Terry Fox Laboratory, British Columbia Cancer Agency, University of British Columbia, Vancouver, British Columbia, Canada [2] Department of Medical Genetics and Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Center for Innovation, Canadian Blood Services, Division of Hematology, Department of Medicine, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Anna
authors.initials: A
authors.lastname: Janowska-Wieczorek
authors.affiliation: Division of Hematology, Department of Medicine, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Joseph
authors.initials: J
authors.lastname: Brandwein
authors.affiliation: 1] Department of Chemical & Materials Engineering, Faculty of Engineering, University of Alberta, Edmonton, Alberta, Canada [2] Department of Biomedical Engineering, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada [3] Faculty of Pharmacy & Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Hasan
authors.initials: H
authors.lastname: Uludag