Gene and genome synthesis through pair-wise ligations of short oligonucleotides

While the fundamental unit of life is the cell, it is the cell’s DNA which instructs how a cell is to function. These microscopic blueprints can be read. Reading DNA sequences has enabled genes to be identified and revealed insights about the causes of many human diseases such as Huntington’s and numerous cancers. Reading and understanding how DNA functions, however, is only half the challenge in genetics research. To correct genetic errors accumulated in diseased genes, it is necessary to also write in DNA. But while DNA is essential in all genetics research, it is difficult to produce. Methods to rewrite or create new DNA sequences from scratch are limited. Regions of DNA can be copied, but there are relatively few methods of generating new fragments. Nucleotides are the characters of the DNA language. A 1,000 nucleotide gene costs approximately $1,000 to construct. Given that the average human gene is more than 3,000 nucleotides long, and that regulatory regions of DNA can be tens of thousands of nucleotides long, the cost of producing DNA becomes daunting. Daniel Horspool is researching a new laboratory technique for DNA construction. While the primary method involves adding one nucleotide at a time chemically to the growing sequence, the new technique relies on stitching multi-nucleotide fragments together in parallel. This process could be much faster and less error prone than the conventional method, and by using microfluidic devices, DNA could be produced at a much lower cost. The research could lead to an approach for constructing complete genes, which would be an important new tool for basic and applied biomedical research. The research could ultimately contribute to efforts to realize the promise of genomic and personalized medicine.