Extremophile RNA Delivery for Radioprotection in Prostate Cancer Patients
Abstract
The number of radiation-treated prostate cancer survivors in the United States is projected to reach 721,000 by 2020. Prostate cancer patients undergoing radiation therapy may experience severe debilitating side effects from treatment. These side effects may manifest as urinary frequency, urinary obstruction, and rectal bleeding, which can reduce a patient’s quality of life significantly. As most prostate cancer patients are cured of their cancer, they may be left with debilitating side effects from treatment, which can result in regret of their treatment decision. Unfortunately, there are very few clinically available drugs or devices that can prevent or reduce these side effects. The purpose of this project is to develop a novel drug delivery device that can be applied directly to the areas of greatest risk to prevent these short- and long-term side effects. This project will utilize engineering tools to enable transient expression of a radiation protection protein that can be used in the form of a gel and patch before radiation treatments. The resulting findings could help reduce the side effects of treatment, leading to a better quality of life for our patients. This proposed technology has minimal risks to patients, as the expression of this protein is transient and there is no genetic modification. Given that this is a new biotechnology, there is much to elucidate regarding safety and efficacy in animals. Upon successfully demonstrating improved radioprotection from the delivery of Dsup mRNA, we will initiate a clinical trial in prostate cancer patients with the opportunity for commercialization. The proposed timeline for impacting patients is approximately 5-10 years. This project will also provide additional insight into new drug and devices for protection from the harmful effects of radiation therapy. This project addresses the FY19 PCRP overarching challenge of improving the quality of life for survivors of prostate cancer. This project was designed around my career research interests, which are to reduce the toxicity of radiation therapy in prostate cancer patients. My major immediate research goal is to develop a radioprotectant to be applied to the urethra and rectum to reduce the risk of developing urethritis and proctitis. Ultimately, the potential of this project and my career goal is to reduce the toxicity of radiation therapy. As I continue to pursue my research interests in the side effects of radiation therapy, I have realized that I need to develop critical skills in drug and device development from design to commercialization and radiation biology in order to become an independent translational researcher and make a significant impact toward reducing the toxicity of radiation in prostate cancer patients. To this end, I have chosen Dr. Anthony D’Amico, a world-renowned prostate cancer expert; Dr. Robert Langer, a chemical engineering and device expert; and Dr. C. Giovanni Traverso, a gastroenterologist and mechanical engineer, as my mentors. Drs. Langer and Traverso have been directly involved in translating devices from the benchtop to the bedside. To acquire the necessary skills and expertise to successfully complete the proposed project and become an independent researcher in this space, Drs. D’Amico, Langer, and Traverso and I have outlined an educational curriculum for me that involves taking coursework in “Innovation and Commercialization” at MIT and “Tumor Pathophysiology: A Systems Biology Approach” at HMS; attending frequent formal scientific workshops offered at MIT, DFCI, and BWH; attending weekly laboratory meetings; and performing mentor-guided studies to address the aims of this project.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010225
Entities
People
- James Byrne
Organizations
- United States Army