Automated long DNA synthesis technology

自动化长DNA合成技术

• 批准号: 8268351
• 负责人: Jingdong Tian
• 金额: $ 38.27万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-27 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8268351
• 关键词: Antibodies; Biological Process; Biological Sciences; Biological Testing; Biomedical Research; Chemistry; Communities; Complex; Cycloparaffins; DNA; DNA Sequence; DNA Sequence Rearrangement; DNA biosynthesis; DNA-Directed DNA Polymerase; Development; Elements; Engineering; Ensure; Enzymes; Evolution; Foundations; Freedom; Gene Components; Genes; Genetic; Genome; Genomics; Goals; Human Biology; In Situ; Lead; Length; Manuals; Metabolic Pathway; Methodology; Microarray Analysis; Microfluidics; Miniaturization; Molecular Biology; Oligonucleotides; Pattern; Pharmacologic Substance; Plastics; Positioning Attribute; Procedures; Proteins; Regulation; Research Personnel; Software Design; Stream; Structure; Surface; Synthesis Chemistry; System; Systems Biology; Technology; Testing; Variant; Writing; base; copolymer; cost; cost effective; design; ds-DNA; endonuclease; expression cloning; flexibility; gene synthesis; human disease; innovation; miniaturize; novel; phosphoramidite; synthetic biology; tool

DESCRIPTION (provided by applicant): The capability of accurate and high-throughput synthesis of long DNA sequences holds the key to ultimate understanding of complex genome organization and function issues. With such capabilities, the identity, position and function of any potential gene and chromosomal regulation elements, many of which are long-range, can be studied by systematically testing the biological effects of designed and synthesized gene or chromosomal sequences. De novo synthesis, instead of simple rearrangements of natural genomic elements, gives researchers total freedom to test the effects of designed novel sequences or fine sequence variations on genome function. However, existing gene synthesis technology still relies on costly and cumbersome macro- scale DNA oligonucleotide synthesis and manual gene assembly procedures. This proposal aims to develop integrated, microfluidics and microarray-based de novo gene synthesis technology platform to fill this gap. This automated gene synthesis platform is able to accurately "write" designed gene sequences into double-stranded DNA molecules, ready for cloning, expression and other down-stream applications. Like thermal cyclers, automated gene synthesizers will be widely used and become an indispensable tool for life science researchers. In addition to genome structure and function studies, the technology will enable many types of biomedical research which are currently difficult or extremely inefficient to perform, such as large scale synthetic genomics, construction of genetic circuits and metabolic pathways, design, evolution and optimization of new proteins, enzymes, antibodies and other pharmaceuticals.

描述(由申请人提供)：准确和高通量合成长DNA序列的能力是最终理解复杂基因组组织和功能问题的关键。有了这样的能力，任何潜在的基因和染色体调控元件的身份、位置和功能都可以通过系统地测试设计和合成的基因或染色体序列的生物效应来研究，其中许多是远程的。从头合成，而不是简单的自然基因组元素的重排，让研究人员完全自由地测试设计的新序列或精细序列变异对基因组功能的影响。然而，现有的基因合成技术仍然依赖于昂贵而繁琐的大规模DNA寡核苷酸合成和人工基因组装程序。该方案旨在开发基于微流控和微阵列的一体化从头基因合成技术平台，以填补这一空白。这个自动化的基因合成平台能够准确地将设计好的基因序列写入双链DNA分子，为克隆、表达和其他下游应用做好准备。与热循环仪一样，自动化基因合成仪将得到广泛应用，成为生命科学研究人员不可或缺的工具。除了基因组结构和功能研究外，该技术还将使目前难以或效率极低的许多类型的生物医学研究成为可能，如大规模合成基因组学、遗传电路和代谢途径的构建、新蛋白质、酶、抗体和其他药物的设计、进化和优化。