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. In the Phase I study, a comprehensive set of experiments validated 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. These included studies in both solution and solid phase, with the Luminex instruments that support multiplexing, and with polymerases. In Phase II, we will prepare 1000 independently binding DNA-like tags, further develop tools to support genotyping of individual patients, and select for polymerases that incorporate both functionalized nucleotides and Aegis components into oligonucleotides.

Proposed Commercial Applications

Chemical systems that support """"""""rule based molecular recognition"""""""" have wide commercial applicability, including in come """"""""blue skies"""""""" (nanotechnology and molecular computing, for example). More immediately, the Aegis system here is supporting a commercial diagnostics system, and has led in the Phase I period to an assay that detects single nucleotide polymorphisms (SNPs). Such assays promise a revolution in predictive medicine and personalized care, with potential market value.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Small Business Technology Transfer (STTR) Grants - Phase II (R42)
Project #
5R42GM063368-03
Application #
6626075
Study Section
Special Emphasis Panel (ZRG1-SSS-Y (10))
Program Officer
Wolfe, Paul B
Project Start
2001-06-01
Project End
2004-05-31
Budget Start
2003-06-01
Budget End
2004-05-31
Support Year
3
Fiscal Year
2003
Total Cost
$250,000
Indirect Cost
Name
Eragen Biosciences, Inc.
Department
Type
DUNS #
City
Madison
State
WI
Country
United States
Zip Code
53717
Johnson, Scott C; Sherrill, Christopher B; Marshall, David J et al. (2004) A third base pair for the polymerase chain reaction: inserting isoC and isoG. Nucleic Acids Res 32:1937-41