Imagine altering gene sequences to prevent or cure a disease. Then imagine the difficulty of pinpointing a gene target in a strand of human DNA, which contains many millions of nucleotide building blocks. If unraveled, the molecules of DNA in just one cell would produce a strand two meters long. If all of a person’s DNA were unraveled, it would create a strand that stretched to the sun and back — 50 times.
UW Medicine bestowed its 2014 Innovator of the Year award on an alumnus attempting to meet the challenge of precision gene manipulation: David Russell, M.D., Ph.D., Fel. ’94, UW professor of medicine in the Division of Hematology.
“Most researchers alter genetic sequences by using enzymes to cut the DNA,” says Russell. “But we don’t think that’s a good idea because it might cause gene mutations or other problems.”
Russell was the first researcher to use a harmless virus vector to deliver a gene to a human cell in a pinpointed location without cutting, a genome-editing technology he patented. He and his team are now using the method to modify human pluripotent stem cells, which can mature into any type of cell tissue in the body. For example, the ability to turn stem cells into heart, liver or brain cells could — in principle —make it possible to treat heart disease, hepatitis or dementia.
Many scientists are using stem cells to create specific tissue types, but moving this work from the lab to the physician’s office is problematic: the body will reject cells it does not recognize as its own. That challenge inspired Russell to change stem cell genes that cause rejection by inactivating them or changing their DNA sequence. The result is a universal stem cell precisely engineered to avoid detection by the immune system.
“This approach will allow us to make one cell line for everyone, which will facilitate getting therapies into the clinic,” Russell says. “If you had to make a new cell line from each patient’s own stem cells, the labor, time, regulatory issues and cost would be totally unreasonable.”
Using a stem cell line developed at UW Medicine, his team can grow an infinite number of universal donor cells that maintain all the instructions needed to mature into any kind of tissue. With a small business grant from the National Institutes of Health, Russell spun out a startup company, Universal Cells, to collaborate with companies and institutions working on clinical stem cell applications. He has been collaborating with UW Medicine teams focusing on heart disease and with the Institute for Stem Cell and Regenerative Medicine, and he hopes to tap into UW Medicine’s strengths in diabetes and blindness.
“We think we have solved a major problem in the stem cell field and created a solution with a powerful future,” Russell says. “It could become a full-circle UW effort — from the creation of the stem cell line through clinical trials — and I would be happy to see it cure even one intractable disease.”