Synthesis and Applications of Boranephosphonate DNA

Problem

Boranephoshonate DNA (bpDNA) is a stable analog DNA where one of the non-bridging phosphate oxygens is replaced by a BH3 group. We discovered the bpDNA reacts with metal ions such as Au3+, Ag+, Pt4+ to produce metallic nanoparticles. When combined with the ability of DNA to base pair to complementary sequences, bpDNA has many promising applications in low-cost diagnostics, electron microscopy probes and for construction of metallic nanomaterials. However, the development of these applications was stunted by a lack of robust chemical synthetic methods. This was a result of the incompatibility of the step to introduce borane into DNA, with the exocyclic amine protecting groups traditionally used in DNA synthesis.

Solution

A research group at CU Boulder, led by Dr. Marvin Caruthers and Dr. Subhadeep Roy, have established a novel silyl-based exocyclic amine protecting group that is compatible with boronation allowing the synthesis of bpDNA oligomers up to 20-25 nucleotide in length in yields and purity comparable to that of unmodified DNA. This technology enables the use of bpDNA in low-cost diagnostics, as well asCRISPR-Cas9 based probes for correlated light electron miscoscopy. These bpDNAs have the advantages of lowering costs, enabling scalable production, and increased chemical stability.

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Dr. Marvin Caruthers was inducted in the 2018 National Inventors Hall of Fame, for developing methods for chemically synthesizing DNA, "a breakthrough that dramatically advanced biological research and helped launch the biotechnology industry." Dr. Caruthers has an impressive background, including an entrepreneurial journey as the co-founder of prominent biotech companies like Amgen and Applied Biosystems.

Market Application

Applications for the technology are areas such as point of care diagnostics, low cost diagnostics, electron microscopy probes and in pathogen detection in test-kits (such as testing for pathogens in food).

What's Next?

The university is looking to outlicense this opportunity to industry partners. This patent portfolio is available for exclusive and non-exclusive licensing.