SBIR Phase I: A Protein Probe for High-Throughput SNP Screening

This Small Business Small Business Innovation Research (SBIR) Phase I research project aims to develop a reagent that binds specifically to DNA mismatches for use in a microarray-based single nucleotide polymorphism (SNP) assay. Directed evolution will be used to isolate variants of a DNA repair protein with substrate binding properties optimized for this assay. Key challenges will be decreasing the affinity for perfectly complementary oligonucleotides and increasing the spectrum of mismatches bound with sufficient specificity. Because this assay does not rely on subtle differences in hybridization energy for detection of mismatch-containing duplexes, the microarrays require only a small number of probes per SNP (2-4) and are not limited to using short probes. The availability of an inexpensive, flexible, and high throughput SNP detection methodology could lead to better understanding of the genetic components of complex diseases and advance the development of personalized medicine where disease prognosis and treatment is individually tailored.