The increasing use of DNA as a molecular tool has ushered the technology of de novo synthesis of DNA back to the center stage of modern biology. We propose the development of a robust, ultra high-throughput (UHT) technology capable of genome-scale production of high fidelity synthetic DNA at about one percent of the cost and time of the current technologies. Our phase I plan will demonstrate the feasibility of the proposed method that includes parallel synthesis of an array of long DNA sequences on a capture microchip using annealing and ligation of assembling deoxyoligonucleotides (oligos). Our Phase I Specific Aims are: 1: Developing a method for parallel synthesis of an array of long DNA sequences on chip; 2: Developing monitoring and error correction methods essential for improving the efficiency and fidelity of the DNA synthesis. The proposed solid phase parallel synthesis technology has two significant advantages over the existing methods of DNA synthesis: (i) it has the potential to allow simultaneous assembling of thousands or more DNA sequences; (ii) it is a process that individual steps and individual synthesis can be monitored and optimized. If successful, one can expect a significant step forward in long DNA sequence preparation, similar to the advancement by moving oligonucleotide and peptide synthesis from solution to solid phase. A reliable, miniaturized, robust process will then replace the current slow, expensive, and still largely unpredictable gene synthesis processes
