With the growing importance of the field of RNA biology, undergraduates need to perform RNA-related research. Systematic evolution of ligands by exponential enrichment (SELEX) has become an important method in RNA biology. The principles of SELEX were applied to a semester-long course-based undergraduate research experience (CURE) in which two rounds of "in vivo" functional selection of regions of a viral RNA were performed. As the labwork had an unknown outcome, students indicated that they were excited by the work and became invested in the experience. By completing two rounds of SELEX, the students repeated molecular methods (e.g., RNA extraction, RT-PCR, agarose gel electrophoresis, DNA purification, cloning, and sequence analysis) and reported that repetition reinforced their learning and helped them build confidence in their lab abilities. Students also appreciated that they did not learn a "technique-per-week" without context, but rather they understood why certain methods were used for certain molecular tasks. Results from a 19-question multiple-choice assessment indicated increased comprehension of theory underlying methods performed. Details regarding experimental methods and timeline, and assessment and attitudinal results from three student cohorts, are described herein.