Student: Elizabeth Delgado
Project Mentors: Dr. Samira Kiani – University of Pittsburgh
Dr. Mo Ebrahimkhani – University of Pittsburgh
Dr. Chris Plaisier – SBHSE
YouTube Link: View the video link below before joining the zoom meeting
Zoom Link: https://asu.zoom.us/j/92489367567
Zoom meeting time: 10am - noon
Abstract
Gene therapy is an increasingly popular and exciting approach to the treatment of previously untreatable diseases. Many have even undergone clinical trials in humans, but there is a still a large amount of concern over the safety of this method. One of the most critically worrisome of these risks is the transmission of germline genome edits which has driven a multitude of scientists to call for a moratorium on germline genome editing. Therefore, it is necessary to ensure complete spatial regulation of gene therapies before further implementing them in human trials where transgenes are delivered into the body. Towards this goal, we evaluated the potential risk of unintentional transmission of synthetic transgenes into the germline of diseased patients. Using a mouse model with LPS-mediated inflammation to parallel the diseased physiology, we delivered a reporter transgene, LacZ, using the popular AAV9 serotype. qRT-PCR analysis of germline cells displayed a direct correlation between the dosage of LPS and AAV9-LacZ and penetrance of AAV9-LacZ. Therefore, due this evidence of increased risk of germline transmission of viral vectors carrying transgenes in diseased patients, we proposed a method for spatial regulation which would disable any synthetic, transgenic system when it reaches germline cells.