The DNA alphabet is not limited to the four standard nucleotides. Rather, twelve nucleobases forming six base pairs joined by mutually exclusive hydrogen bonding patterns are possible within the geometry of the Watson-Crick base pair. These form An Expanded Genetic Information System (AEGIS), a new, """"""""rule based"""""""" molecular recognition system that carries protein functionality, can be prepared in combinatorial form, and can be copied much like nucleic acids. Given the rich understanding of this system after a decade of research in the Benner laboratory, AEGIS is a technology transfer opportunity. This STTR grant will facilitate the direct transfer of technology developed in the Benner laboratories to EraGen Biosciences. In the Phase I study, a comprehensive set of experiments will validate the ability of AEGIS to provide a set of orthogonal, non-cross reacting tags useful to support highly multiplexed (100 or more analytes) DNA diagnostics systems. In Phase II, we will implement a process based on chips and/or Luminex beads to simultaneously detect several hundred genetic traits per sample. This work will set the stage for a Phase III launch in 2002 of an instrument for determining which of a large number of defective/polymorphic DNA molecules are found in a sample of biological tissue.
The technology discussed here, An Expanded Genetic Information System (AEGIS) has already been applied in diagnostics systems that test for the presence of a single oligonucleotide. Here is converted a product with no commercial potential to one that generates $150 MM annually. As multiplexing is essential for any tool to do customized genotyping as the asis for individualized therapy, and as AEGIS technology is effectively the only system that generates tags following simple rules that are orthogonal to natural DNA, the impact of the technology on diagnostics in the 21st century should be extremely broad.
| Chen, Fei; Gaucher, Eric A; Leal, Nicole A et al. (2010) Reconstructed evolutionary adaptive paths give polymerases accepting reversible terminators for sequencing and SNP detection. Proc Natl Acad Sci U S A 107:1948-53 |
| Fukami-Kobayashi, K; Schreiber, D R; Benner, S A (2002) Detecting compensatory covariation signals in protein evolution using reconstructed ancestral sequences. J Mol Biol 319:729-43 |
