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Scott, Mark
Senior Scientist
Centre for Innovation – Canadian Blood Services
Investigator
Centre for Blood Research – University of British Columbia
Clinical Professor
Pathology and Laboratory Medicine – University of British Columbia
Education
- Doctor of Philosophy in Pathology and Laboratory Medicine, University of Minnesota, Minneapolis, Minnesota, USA
- Master of Arts in Science, Western State Colorado University, Gunnison, Colorado, USA
- Bachelor of Arts in Biology and Psychology, Western State Colorado University, Gunnison, Colorado, USA
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Use of Immunocamouflaged Cells in Transfusion and Transplantation Medicine
Dr. Mark Scott has pioneered the immunocamouflage of red blood cells, leukocytes and platelets. This novel, patented technology relies on the chemical attachment of biologically safe polymers on cell membranes to camouflage cell surface antigens.
Why is this important?
Immunocamouflaged cells and tissues hold great therapeutic promise in transfusion and transplantation medicine. For example, immunocamouflaged red blood cells could meet the often urgent needs of chronically transfused patients who have alloimmunization and for whom matched donors can be nearly impossible to find. Dr. Scott’s research has yielded over 20 issued and pending patents in the fields of bioengineering, hematology, immunology, virology and redox biology.
Immunocamouflage is a non-immunogenic barrier that prevents the recognition of antigenic sites on the cell membrane by pre-existing antibodies - hence preventing immunological rejection - and significantly diminishes the immunogenicity of the foreign cellular epitopes. Ongoing projects within the laboratory include the modification of red blood cells to prevent alloimmunization in the chronically transfused (e.g., sickle cell, thalassemic, autoimmune hemolytic anemia) patient; the prevention of graft versus host disease via lymphocyte modification; the induction of tolerance by pre-exposure to immunocamouflaged allogeneic cells; and the modification (PEGylation) of platelets to enable their storage at 4 °C. Currently, platelets must be stored at room temperature since transfusion of cold storage-activated platelets leads to rapid clearance of these cells within the recipient. Cold storage could prolong the shelf-life of platelets and improve their safety by minimizing bacterial growth.
Selected Publications
- Kyluik-Price DL, Li L, Scott MD: Effects of Methoxypoly (Ethylene Glycol) Mediated Immunocamouflage on Leukocyte Surface Marker Detection, Cell Conjugation, Activation and Alloproliferation. Biomaterials 2016; 74:167-177.
- Li L, Noumsi GT, Kwok YYE, Moulds JM, Scott MD: Inhibition of Phagocytic Recognition of Anti-D Opsonized Rh D+ RBC By Polymer-Mediated Immunocamouflage. American Journal of Hematology, 2015; 90:1165-1170.
- Scott MD: ResearchUnit: Using immunocamouflage to fool the immune system. 2015; Blood.ca website.
- Kyluik-Price DL, Li L, Scott MD: Comparative efficacy of blood cell immunocamouflage by membrane grafting of methoxypoly(ethylene glycol) and polyethyloxazoline. Biomaterials 2014; 35:412-422.
- Wang D, Toyofuku WM, Scott MD: The potential utility of methoxypoly(ethylene glycol)-mediated prevention of Rhesus blood group antigen RhD recognition in transfusion medicine. Biomaterials 2012; 33:3002-3012.
- Wang D, Toyofuku WM, Chen AM, Scott MD: Induction of immunotolerance via mPEG grafting to allogeneic leukocytes. Biomaterials 2011; 32:9494-9503.
- Scott MD, Murad KL, Koumpouras F, Talbot M, Eaton JW: Chemical camouflage of antigenic determinants: “Stealth” erythrocytes. Proc. Nat. Acad. Sci. USA 1997; 94:7566-7571.
Polymer-Based Antiviral Gel
Immunocamouflage also has application in the inactivation of viruses and/or prevention of viral infections.
Why is this important?
Viral infections are difficult to prevent due to our inability to effectively vaccinate against most viruses. Dr. Scott’s research has led to the development of an antiviral gel that, unlike vaccinations, is effective against a broad spectrum of viruses.
Studies in Dr. Scott’s laboratory have demonstrated that the immunocamouflage of the cell prevents viruses from infecting the cell. Based on this, we have developed an inexpensive broad spectrum anti-viral gel that can be use prophylactically and provides immediate protection against a broad range of viruses, unlike vaccinations. The prophylactic gel is easy to apply (e.g., intranasal application) and gives significant protection against viral infection for at least 48 hours post application. The utility of this technology towards respiratory (e.g., rhinoviruses) and blood-borne viruses is under active investigation.
Selected Publications
- Kyluik DL, Sutton TC, Le Y, Scott MD: Chapter 7: Polymer-mediated broad spectrum antiviral prophylaxis: utility in high risk environments. In: Progress in Molecular and Environmental Bioengineering - From Analysis and Modeling to Technology Applications (Editor: Carpi A.) Intech, ISBN 978-953-307-268-5. 2011; pp.167-190.
- Sutton TC, Scott MD: The effect of methoxypoly(ethylene glycol) chain length on the inhibition of respiratory syncytial virus (RSV) infection and proliferation. Biomaterials 2010; 31:4223-4230.
- McCoy LL and Scott MD: Broad spectrum antiviral prophylaxis: Inhibition of viral infection by polymer grafting with methoxypoly(ethylene glycol). In: Antiviral Drug Discovery for Emerging Diseases and Bioterrorism (Editor: Torrence PF) Wiley & Sons, Hoboken, NJ. 2005; pp.379-395.
Serum-Derived microRNA Therapeutics
The third major area of interest in Dr. Scott’s laboratory has been the development of microRNA (miRNA) based biologics for the treatment and prevention of autoimmune diseases.
Why is this important?
Current immunosuppressive drugs exhibit high toxicity and unwanted side effects. These natural, blood serum derived, miRNA-based therapeutics exhibit low toxicity and yet provide potent immune regulatory effects that may be useful in treating a broad range of autoimmune diseases.
miRNA are small ribonucleic acid sequences that used to be thought of as ‘cellular debris’. However, we now know that these miRNA exert potent regulatory roles in all animals. Dr. Scott’s laboratory has developed a process by which miRNA can be produced from serum that has therapeutic benefit. The patent-pending miRNA-therapeutics were derived from Dr. Scott’s previous research on the prevention of transfusion-associated graft versus host disease (TA-GVHD) - a rare, but serious consequence of white blood cells present in transfused blood products. On-going studies on the plasma-derived therapeutics demonstrate their efficacy in preventing inflammatory reactions and in the inhibition of experimental murine autoimmune Type 1 Diabetes.
Selected Publications
- Wang D, Shanina I, Toyofuku WM, Horwitz MS, Scott MD: Inhibition of Autoimmune Diabetes in NOD Mice by miRNA Therapy. PlosONE, 2015; In Press.
- Wang D, Toyofuku WM, Chen AM, Scott MD: Induction of immunotolerance via mPEG grafting to allogeneic leukocytes. Biomaterials 2011; 32:9494-9503.
For general enquiries about research at Canadian Blood Services, please contact us at:
Centre for Innovation
Canadian Blood Services
1800 Alta Vista Drive
Ottawa, Ontario K1G 4J5