CAREER: Multifunctional Polymer Coatings of Virus Particles for Safer and More Efficient Gene Delivery

Oklahoma State University, Stillwater OK

Investigators

Abstract

This CAREER award to Oklahoma State University by the Biomaterials Program in the Division of Materials Research is to investigate how the material properties of multifunctional and aptamer-derivatized polyethylene glycol-grafted-polylysine copolymer would affect the gene delivery efficiency of a polymer/adenovirus vector. Earlier studies have shown that a hybrid vector possesses advantages over current viral and nonviral vectors. Determining how the hybrid vector could be further improved to better mimic the efficiency of a viral vector with none of the drawbacks, however, remains a significant challenge. The proposed study is expected to provide new insight into the design of hybrid, and eventually, non-viral gene delivery vectors. This in turn would guide the development of new materials to overcome current bottlenecks in the gene delivery system. These expected outcomes will be achieved by comparing the mechanisms by which the hybrid vector and native adenovirus transform cells and comparing the efficiency and rate at which the viral and hybrid vectors deliver genetic material. Through these efforts, the research investigator will be able to determine limitations of the currently used materials and would provide a better understanding of how to design material properties to overcome the current limitations. The proposed outreach activities would also directly impact Native American, African American and homeschooled students in exposing them to STEM related topics and would encourage them in STEM related higher studies and careers. Further, the proposed broader impact activities included assistance to school teachers in developing laboratory practices and curriculum development, thereby encouraging students to see the ways in which science and engineering shape their future. As part of teaching, training and education, the graduate and undergraduate students in cutting-edge research techniques for discovering and studying novel biomaterials. Gene therapy has long promised to change the way we prevent and treat disease in this country. The field, however, has largely failed to advance beyond the clinical trial stages due to difficulties encountered in delivering genes in a safe and efficient manner. The focus of this project would be in discovering and characterizing novel biomaterials that would help to transition from virus-based delivery methods to synthetic particle-based delivery methods. The project will develop a hybrid polymer/virus delivery method to help better understand how these materials would affect gene delivery. The project is expected to improve the basic understanding on how to design novel materials for gene delivery that will potentially transform the field from a fringe medical treatment to common practice. The project will also help train the next generation of scientists and engineers by working with high school teachers in integrating biomaterials teaching and training into current curriculum and laboratory practices. The project also involves two-week summer research studies in the PI's laboratory, primarily intended for Native American, African American and home-schooled high school students.