Engineered advances for clinical applications of gene therapy

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Blood cell production is a complex multi-step process that originates in a rare subpopulation of self-maintaining stem cells. Significant interruption of blood cell production activates these stem cells and stimulates them to regenerate the system. Most of the blood stem cells normally reside in the bone marrow, but they do also spontaneously enter the blood stream and then return to the bone marrow. The latent regenerative activity of blood stem cells in combination with their ability to efficiently re-home to the bone marrow following intravenous injection are the basis of bone marrow transplant therapies now in clinical use worldwide. A powerful application of this approach is to harvest stem cells from patients with genetic disorders, correct the defect "ex vivo" and then attempt to cure the patients by transplanting them with their own, corrected stem cells. This type of stem cell-based gene therapy strategy offers the potential of enormous benefit to many patients with congenital disorders like 6-thalassemia and sickle cell disease - 2 inherited diseases that adversely affect the lives of millions of people around the world. However, significant hurdles continue to prevent stem cell-based gene therapies from becoming a practical clinical procedure. Blood stem cells are transduced very inefficiently and they also differentiate rapidly as soon as they are placed in culture. To address these issues, a unique team of bioprocess engineers and stem cell medical researchers will evaluate and bring forward several novel reagents they have recently identified as able to circumvent these problems in model systems. The success of this project will thus greatly advance the possibility of permanent cures for patients with a wide variety of blood disorders that afflict thousands of Canadians and their families, and for which there are currently no known alternatives beyond palliative treatments.