Gene Editing Aims to Control T1D
Benaroya Research Institute (BRI) and Seattle Children’s Research Institute (SCRI) are pioneering the use of gene editing techniques in efforts to control type 1 diabetes (T1D). “This research could be an enormous asset in developing future therapies for many autoimmune diseases like type 1 diabetes, multiple sclerosis, rheumatoid arthritis and more,” says BRI President Jane Buckner, MD.
Dr. Buckner, BRI’s Gerald Nepom, MD, PhD, SCRI’s Director of the Center for Immunity and Immunotherapies David Rawlings, MD, and SCRI’s Andrew Scharenberg, MD, are the lead investigators of the $1 million grant from The Leona M. and Harry B. Helmsley Charitable Trust.
“This is a preclinical study in the laboratory where we take cells that recognize the pancreas from people with type 1 diabetes,” explains Dr. Buckner. “We engineer or edit the genes in the cells so they become regulatory T cells. Importantly, they will remain regulatory T cells in the body so we can use them therapeutically. The long-term goal would be to take cells from a person who has type 1 diabetes or is at high risk for the disease. We would remove cells from their blood, edit the cells that would attack the islet cells in the pancreas and turn them into regulatory T cells. Then we would inject them back into the patient’s bloodstream, and they would travel to the pancreas and stop any T cell attacks in the pancreas.
“This research could lead to fundamentally new ways to prevent loss of immune system regulation, a common problem in autoimmune diseases like type 1 diabetes where the body’s own immune system attacks and destroys the islet cells in the pancreas that make insulin,” says Dr. Buckner. People with type 1 diabetes must inject themselves with insulin in order to stay alive.
BRI and Seattle Children’s have collaborated on numerous projects. In this study, BRI brings its regulatory T cell expertise to combine with SCRI’s gene editing expertise to attack this complex problem. Previously in laboratory testing, BRI scientists discovered a means to create regulatory T cells that have the potential to control unwanted immune responses such as those that lead to autoimmune diseases. The scientific team used tetramer technology, developed by BRI, to identify and purify small populations of white blood cells that can be converted to T regulatory cells. Scientists recently found that these regulatory T cells lose their effectiveness over time and are now looking for a way to maintain the cells as regulatory T cells through gene editing.
T Cell Therapy
Regulatory T cells are white blood cells that can block the activation of other harmful T cells and thus regulate the immune system, avoiding autoimmune diseases. The benefit of using regulatory T cells for therapy is that it can focus immune suppression on a specific area without impairing the entire immune system, a key objective for treating and curing autoimmune diseases. Currently, most immune therapies are not very targeted and suppress the body’s entire immune system, leaving the body vulnerable to infections, bacteria and viruses.