CAREER: mON-SHOT : Training Environmental Engineers to Track the Fate of Emerging Therapeutic Modified Oligonucleotides

Using modified short strands of genetic material, known as oligonucleotides, to treat disease is revolutionizing medicine. Many different types of oligonucleotides are being used to treat common and rare diseases. These therapeutics remain active and stable in the body. Some pass through patients into wastewater systems. However, there are no tools available to track these genetic materials in water systems or to guide wastewater treatment approaches. This project will develop methods to detect these new pharmaceuticals in wastewater, study how they break down, and design treatment systems to remove them. The project will also train engineers in molecular biology skills needed to manage genetic material in the environment through a new undergraduate course, industry workshops, and a graduate student podcast series. Together, these efforts will prepare engineers to manage the increasingly important intersection of biotechnology and water infrastructure. This project will advance a new conceptual framework and analytical methodology for monitoring short, modified oligonucleotides in the environment. The project will develop advanced quantitative polymerase chain reactions optimized for wastewater. These tools will identify how structural modifications of the oligonucleotides drive persistence and how molecular hybridization influences fate in direct wastewater bioassays. Unlike conventional small-molecule fate models, this research will emphasize biomolecular interactions, specifically hybridization with environmental nucleic acids. Hybridization can act as a barrier or enhancement to degradation, representing an underexplored fate pathway within wastewater. The project will couple these experimentally derived fate parameters with pharmaceutical use data to model sewer network concentrations and evaluate activated sludge treatment performance, supporting better management of these biotechnology byproducts in the built environment. Education activities will leverage this research infrastructure directly: a freshman bio-design course will use project-developed assays as teaching tools, industry workshops will disseminate modeling frameworks for assessing infrastructure vulnerability, and graduate researchers will develop communication skills while producing podcast content on the interface between biotechnology and the environment. This integrated approach will establish a framework for anticipating how emerging bioproducts enter and persist in water systems and will support advances in biotechnology This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria. NSF Award ID: 2542554 | Program: 01002627DB NSF RESEARCH & RELATED ACTIVIT | Principal Investigator: Cresten Mansfeldt | Institution: University of Colorado at Boulder, Boulder, CO | Award Amount: $597,676 View on NSF Award Search: https://www.nsf.gov/awardsearch/show-award/?AWD_ID=2542554 View on Research.gov: https://www.research.gov/awardapi-service/v1/awards/2542554.html