Viruses have the natural capacity to deliver DNA into host cells - a powerful ability that is currently being leveraged for a variety of gene therapy applications, including for the treatment of cancer, Alzheimer's disease, and a variety of pediatric genetic diseases. The safety and efficacy of these gene therapies ultimately rely on the ability of viruses to deliver the DNA to the correct tissues and to the appropriate levels without hitting non-target organs. This targeted and controlled delivery of therapeutic DNA by viruses is a tremendous hurdle that, once overcome, will enable the clinical translation of a greater number of life-saving cures. The NSF project aims to approach this overarching goal by developing viruses that can be controlled by safe, externally applied light. Using light as the "on" signal, the infectivity of therapeutic viruses will be carefully controlled in order to deliver the DNA to the desired tissues and to the therapeutically appropriate levels. The associated educational activities will broaden the participation of underrepresented minorities in science and technology. Specifically, predominantly African-American high school students from a critically underserved community in Houston, Texas will be introduced to scientific research and provided career mentorship. Undergraduate students will also be trained to conduct primary scientific research in the Principal Investigator's (PI's) lab. Finally, graduate students in the PI's lab will be highly encouraged to partake in the numerous outreach activities available to them through the PI's lab as well as other Rice University organizations. By training the next generation of scientific leaders to become conscientious of issues relating to gender and/or race, the PI hopes to contribute to our collective future where gender and race are no longer issues to be dealt with in STEM fields.
Viruses have evolved to deliver genetic information into host cells, a key property currently being exploited for applications ranging from fundamental discovery studies to human gene therapy. However, more advances are required to transform naturally occurring viruses into well-controlled and predictable nanodevices. To this end, this NSF project will place viral gene delivery under the control of an externally applied stimulus, specifically light, such that transgene expression may exhibit more tunable intensity, controlled onset/duration, and spatial patterning. Importantly, results obtained from the work will help uncover new design rules for creating stimulus-responsive viral nanoparticles. Promising pilot data demonstrates successful generation of a prototypic light-activatable virus (LAV) platform. To overcome some of the deficiencies with the prototype platform that would hinder its translation to real world settings, this NSF project aims to generate second generation LAVs. The LAV candidates will be characterized for various structural and functional properties, enabling the further identification of design rules that may help inform future design modifications to the LAV platform. As part of the educational plan, the PI proposes to develop a STEM mentorship program between Rice University Institute of Biosciences and Bioengineering and a high school located in one of the lowest income areas in the City of Houston, Texas. Additionally, undergraduate students will be recruited to the PI's laboratory to conduct research, and graduate students in the PI's lab will be trained as future leaders conscientious of gender and race issues in STEM fields. The students participating in the research will be trained at the unique interface of virus engineering and synthetic photobiology. The knowledge gained from the work will be widely disseminated through presentations at international conferences and publications in peer-reviewed journals.
