Parallel DNA Assembling on MicroChip

描述（由申请人提供）：越来越多地使用DNA作为分子工具，将DNA的从头合成技术带回了现代生物学的中心舞台。我们建议开发一种强大的，超高通量（UHT）技术，能够在基因组规模上生产高保真合成DNA，成本和时间仅为当前技术的1%左右。我们的第一阶段计划将证明所提出的方法的可行性，该方法包括利用退火和连接组装脱氧寡核苷酸（oligos）在捕获微芯片上平行合成一组长DNA序列。我们第一阶段的具体目标是：1：开发一种在芯片上平行合成长DNA序列阵列的方法；2：发展对提高DNA合成效率和保真度至关重要的监测和纠错方法。与现有的DNA合成方法相比，所提出的固相平行合成技术具有两个显着优点：(i)它具有允许同时组装数千或更多DNA序列的潜力；（ii）它是一个可以监测和优化单个步骤和单个合成的过程。如果成功，人们可以期待在长DNA序列制备方面迈出重要的一步，类似于将寡核苷酸和肽合成从溶液转移到固相的进步。一种可靠的、小型化的、健壮的过程将取代目前缓慢、昂贵、仍然难以预测的基因合成过程。

DESCRIPTION (provided by applicant): 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.