STTR Phase I: A Non-Chromatographic Technique for Synthetic Oligodeoxynucleotide Purification

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The broader impact/commercial potential of this Small Business Technology Transfer (STTR) project will be the development of a novel method for synthetic oligodeoxynucleotide purification. Currently, most oligodeoxynucleotides are purified using chromatography. The techniques are expensive or difficult to scale up, and unsuitable for parallel purification of multiple different samples. The proposed technology is easy to scale up for large-scale purification and suitable for parallel purification. Several areas that require synthetic oligodeoxynucleotides will benefit from the technology including oligodeoxynucleotide therapeutics and oligodeoxynucleotides used in genome assembly for synthetic biology applications. For therapeutic manufacturing, the proposed technology is expected to bring down the cost of production. For synthetic biology, the bottleneck is in the area is de novo construction of genomes, which requires large numbers of synthetic oligodeoxynucleotides. Parallel purification using the proposed technology will make these materials more affordable. In addition, the proposed technology can be readily extended to purify other biooligomers including peptides and oligosaccharides. This extension will have a high impact in areas such as biomedical research. This STTR Phase I project proposes to method for synthetic oligodeoxynucleotide purification based on the "catching by polymerization" concept for the purification of synthetic oligodeoxynucleotides. Currently, most synthetic oligodeoxynucleotides are purified using chromatography methods, which rely on the rate of speed difference at which product and impurities travel in a solid matrix when eluted with solvents for separation. Drawbacks include expensive instrumentation, intensive labor, use of large volumes of harmful solvents and inability to purify long sequences. This method is expensive to scale up and unsuitable for parallel purification. This project aims to commercialize the catching full-length sequence by polymerization oligodeoxynucleotide purification technology to solve these problems. The method works by selectively tagging a polymerizable group to the oligodeoxynucleotide product, polymerizing it into an insoluble polymer, washing away all impurities and then cleaving the product from the polymer. Because the principle on which the product is separated from impurities is drastically different from that of chromatography methods, the proposed technique has many advantages, which include no need for expensive instrumentation, simple-to-use, low waste to product ratio, and suitability for purification of long sequences. Additionally, the new technique is readily scalable for large-scale purification, and can be easily adopted for parallel purification.