Non-viral delivery of Crspr gene therapy to the liver with microbubbles

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Gene therapy has great promise for treating genetic diseases, and even for more common diseases such as atherosclerosis. Over the past decade the technology of Crspr has allowed scientists to fix individual errors in the genetic code that cause disease. Gene therapy would be easier if we had a way to deliver the genes without using viruses or invasive methods. In the Center for Cardiovascular Research at the John A. Burns School of Medicine, former graduate student and postdoctoral researcher, Dr. Cynthia Anderson, has made a step towards that goal. In a recently published paper she describes using ultrasound and microbubbles to deliver Crspr “tools” to the liver to modify a gene that is important in maintaining cholesterol levels.

Working with her mentor, Dr. Ralph Shohet, and collaborators at Stanford University, Anderson mixed plasmids that encode the proteins and DNA needed to change a gene sequence with microbubbles that are commonly used for contrast in echocardiography. She injected this mixture into mice and exposed the liver to high intensity focused ultrasound as the bubbles moved through the liver. When the bubbles popped the plasmids were transferred to the liver cells. There they changed the genetic code of the PDE3B gene in a way that inactivated the protein. This inactivation is known to lower triglyceride levels and to protect against cardiovascular disease in humans. Anderson also showed that, in this proof-of-principle experiment, that changing DNA sequence in the living animal was less accurate than in cell culture, using the exact same Crspr plasmids. This is important as we often evaluate the effects of gene therapy first in cell culture, and Anderson's experiment emphasizes that we need to be particularly careful of how the same therapies will work in animals, and eventually in humans. 

Published in Molecular Therapy-Nucleic Acids, read the full report here.