Synthesis of Difficult Genes: Automation with Microfluidics
Develop an integrated microfluidics platform to significantly reduce the cost and complexity of building long, complex DNA fragments using ligation assembly.
Sponsor: Gen9, Inc. (formerly Codon Devices, Inc.)One Kendall Square
Cambridge, MA 02139
Advances in gene synthesis—building custom-made DNA fragments—are revolutionizing modern biotechnology with new tools for studying proteins, creating antibodies and more. This has been driven by technological innovations in the construction of large DNA fragments (greater than 300 base pairs). In the past four years, the cost to synthesize a large DNA fragment has dropped by a factor of nine, and the turnaround time reduced by two-thirds, largely as a result of automation and process improvements in the use of PCR (polymerase chain reaction) to assemble DNA. Unfortunately, not all gene sequences can be manufactured using a PCR-based assembly process. Several types of gene sequences are known to fail in PCR assembly, including those with regions of high repetition of sequences and those with many occurrences of certain amino acid combinations. In these cases, the sequences must be built using ligation, a process that is much more labor and resource intensive. Ligation typically costs six to 10 times as much as PCR assembly. Codon Devices has proposed developing an integrated microfluidics platform which could reduce the cost of ligation assemblies significantly. The microfluidics approach will address many of the limiting and cost-prohibitive elements of ligation assembly. The technology platform also would make gene synthesis available on researchers' benches as a stand-alone instrument for the first time. A microfluidic platform for ligation-based assembly of genes would greatly advance the state of the art in gene synthesis and help the United States retain its lead in biotechnology and biosafety.