CAREER: Encrypted Virus Nanoparticles for Targeted Gene Delivery

William Marsh Rice University, Houston TX

Investigators

Abstract

ID: MPS/DMR/BMAT(7623) 0955536 PI: Suh, Junghae ORG: Rice University Title: CAREER: Encrypted Virus Nanoparticles for Targeted Gene Delivery INTELLECTUAL MERIT: Delivering nucleic acid-based therapeutics into target cells specifically is a considerable challenge. Current approaches to achieving targeted gene delivery are limited to modifying the delivery vectors to recognize particular cell surface receptors. Unfortunately, in certain diseases, such as breast cancer, chances of finding a specific cell surface biomarker that identifies all cancer cells are low. Thus, a therapeutic that targets a single cell surface receptor will likely face difficulties in achieving specificity. As a potentially superior alternative approach, the PI proposes to develop innovative virus based gene delivery vectors that are able to compute multiple biomolecular signatures, which in combination are unique to breast cancer, to achieve improved targeting and delivery of nucleic acid therapeutics into breast cancer cells. The virus nanoparticles will be programmed to detect the presence of enzymes misregulated in cancer. A collection of virus nanoparticles encoded with high levels of biomolecular encryption will be developed. The nanoparticles will "unlock" only upon sensing the correct combination of enzymatic inputs preset for identity and intensity. Only successfully unlocked virus capsids will go on to deliver their therapeutic payload into the cell nucleus. Rational and combinatorial design approaches will be used in synergy to engineer virus scaffolds whose bioactivities are actuated by single inputs or by dual inputs under a defined Boolean logic operator. Such sophisticated gene delivery vectors should yield improved therapeutic outcomes. The impact of this research extends far beyond the gene delivery field. The creation of advanced genetically encoded nanoparticles that are able to sense complex stimuli and respond with desired programmed functions can be used as the active components of a number of technologies that already depend on the capabilities of nanoparticles. Nanomaterials able to conduct such complex biomolecular information processing can be very useful for numerous applications, ranging from biomedicine to national defense. This novel technology will enhance the current technical possibilities of nanoscale devices. BROADER IMPACTS: The PI proposes a highly integrated high school to graduate level training, education, and outreach program centered on educating students about viruses and their exciting place in bionanotechnology. Diversity has been incorporated with care throughout the research and educational plan. The PI will leverage the developed networks of several key organizations, including NSF-funded Center for Biological and Environmental Nanotechnology (CBEN) and Alliances for Graduate Education in the Professoriate (AGEP), to reach large numbers of underrepresented students through lectures, informal lunch meetings, and lab tours and demonstrations. High school and undergraduate students will be exposed to the emerging technologies built from viruses and will be given the opportunity to conduct research in the PIs laboratory. The PI will provide extensive mentorship to students to guide them towards a successful future in science and engineering. Knowledge and inventions derived from the PIs research will be incorporated into a new graduate level course, "Viruses for Bionanotechnology", as well as into the lectures aimed at high school and undergraduate students. Importantly, the PIs graduate students will be trained to become conscientious future mentors aware of the importance of diversity.