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.

Public Health Relevance

This proposal aims to develop accurate automated and low cost de novo gene synthesis technology platform. Such a technology would be extremely useful for studying complex genome organization and function issues. In addition, the technology will enable many types of biomedical research which are currently difficult or extremely inefficient to perform, and will lead to better understanding of human biology and diseases.

National Institute of Health (NIH)
National Human Genome Research Institute (NHGRI)
Research Project (R01)
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Instrumentation and Systems Development Study Section (ISD)
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Schloss, Jeffery
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Duke University
Biomedical Engineering
Schools of Engineering
United States
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Quan, Jiayuan; Tian, Jingdong (2014) Circular polymerase extension cloning. Methods Mol Biol 1116:103-17
Ma, Siying; Tang, Nicholas; Tian, Jingdong (2012) DNA synthesis, assembly and applications in synthetic biology. Curr Opin Chem Biol 16:260-7
Saaem, Ishtiaq; Ma, Siying; Quan, Jiayuan et al. (2012) Error correction of microchip synthesized genes using Surveyor nuclease. Nucleic Acids Res 40:e23
Ma, Siying; Saaem, Ishtiaq; Tian, Jingdong (2012) Error correction in gene synthesis technology. Trends Biotechnol 30:147-54
Quan, Jiayuan; Saaem, Ishtiaq; Tang, Nicholas et al. (2011) Parallel on-chip gene synthesis and application to optimization of protein expression. Nat Biotechnol 29:449-52