In another example of the recent affinity between microarray manufacturers and the US government’s Defense Advanced Research Projects Agency (DARPA), Agilent Labs has signed a $6.1 million, three-year gene synthesis research agreement with DARPA and the University of Colorado.
The project, which will be jointly funded by Agilent and DARPA, is aimed at developing a novel gene synthesis technique that could make fabrication of nucleic acid probes for microarrays cheaper, simpler, and safer.
This announcement follows Orchid Biosciences’ September award of a three-year, $4.8 million contract from DARPA to develop microfluidic-enabled synthesis of long oligonucleotides. Motorola also announced in February that it had been awarded a $5 million DARPA contract to develop its microfluidic Multi-Chip-Module genetic analysis sample preparation systems.
As DARPA has shown a recent flurry of interest in DNA synthesis and analysis technologies, biochip companies have looked to the agency for R&D funding of projects that also have long-term potential to enhance their technology for civilian uses.
In this project, Agilent’s Doug Dellinger will collaborate with Marvin Caruthers, the University of Colorado chemist who developed currently used gene synthesis technologies over 20 years ago. While these techniques rely on a four-step process that requires toxic reagents, the new method under development would halve the time needed to complete the procedure, reducing it to two steps and replacing many dangerous solvents.
Agilent has worked with the University of Colorado for several years on developing and improving this method, said Steve Laderman, manager of the molecular diagnostic department at Agilent Laboratories. The DARPA grant will further develop and extend the project.
Certain rights to the technology will be retained by DARPA, and the rest will be divided between the University of Colorado and Agilent.
A more straightforward process for nucleic acid synthesis would improve oligonucleotide synthesis, accelerate and simplify microarray manufacture, and could eventually dovetail with Agilent’s microfluidics work, said Laderman.
“We believe we’re in the forefront of this approach,” he said. “The real value is the improvement that we hope it’ll make in our products. Our hope is that the technology will increase the performance as well as simultaneously lower the manufacturing costs.”
Laderman said this effort was in part driven by new chemical insights that make the technique possible, and in part by the demand for improved synthesis techniques.
“It’s a matter of having a combination of a deep understanding of the chemistry associated with the chemical synthesis of DNA, [and] what challenges we face today in going to very microscale synthesis,” he said. “Those challenges differ from the ones faced 20 years ago.”
“DARPAcogenomics”: The Right Office for the Right Project
Currently, DARPA’s Advanced Technology Office is sponsoring a microelectronics and bioprocesses program, which has the goal of developing new technologies for manufacturing, manipulating, and amplifying oligonucleotides. This Agilent Labs-University of Colorado project and the Orchid effort both received their funding from this program. The agency has said its budget for this program would not exceed $5 million for fiscal year 2001, $8 million in FY 2002, $11 million in FY 2003, and $7 million in FY 2004.
DARPA’s Office of Special Projects has also funded R&D into microarrays as part of its two-pronged Sensors for Bioagents program. The component technologies prong of the program has funded research to develop a phylogenic microchip with over 100 oligonucleotide probes for signature sequences of different organisms, allowing rapid identification of unknown samples. It has also sponsored research into upconverting phosphors, a next-generation technology to replace fluorescent labels, as well as high-affinity, high-specifity moieties that could replace antibodies as biodetection probes. The Sensor Integration and Modeling for Biological Agent Detection prong of the program has funded research into a whole panoply of post-genomic technologies, from mass spectrometry to amplification-based sensors.
Finally, the agency’s Microsystems Technology Office has sponsored the BioFlips program to design microfluidics systems that serve as on-chip sample-to-answer biological fluid assays for monitoring and controlling the person’s (soldier’s) health parameters. The Motorola project is part of this program.