The Coalescence of the Next Generation of DNA Reading and Writing

The knowledge about biological systems together with powerful synthesis technologies turn DNA increasingly into a subject of design. However, the setup of synthetic biological systems involving millions of bases is still limited by the accuracy of chemical DNA synthesis and misassemblies in complex DNA mixtures. New high throughput DNA sequencing (reading) and massively parallel oligonucleotide synthesis (writing) have brought down costs by 3 to 4 logs but have not yet been used in combination to impact high-throughput synthetic genomics. We describe here a way to merge these next generation strategies. Our "Megacloning" technology involves microarray based oligonucleotides synthesis and retrieval of sequenced DNA from a Next Generation Sequencing (NGS) device. This approach reduces error rates by three orders of magnitude and is capable of producing 1 Mbp sequenced DNA within days. In principle, up to billions of DNA fragments can be sequenced, characterized and sorted in a single Megacloner run, enabling many new applications.