designing genomes from scratch will be the next revolution in biology.

TheScientist | A little over one year ago, my team at the J. Craig Venter Institute announced the construction of the first cell completely controlled by a synthetic genome. After 8 years of work on DNA synthesis, assembly, and error correction, and on new ways to transplant and boot up chromosomes, we succeeded in creating a cell that used only a chemically synthesized chromosome to code for all aspects of the cellular phenotype.

DNA is the software of the cell, and our studies have shown that when we change the software we change the species. Because it is based on the digitized DNA sequence, the design of synthetic genomes provides a true interface between the computer and biological life. While genome design will dominate the future, the field has been limited to a few gene changes as a part of pathway design and to the engineering of novel biological circuits, such as oscillators, that can be used to construct semisynthetic biological machines.

One major limitation is the cost—in both money and time—associated with genome modification. For example, it required over a decade of work and reportedly more than $100 million for the team at DuPont to make a dozen or so modifications to the E. coli genome so that it would convert glucose into propanediol to make “renewably sourced” fibers. And while some clever techniques for codon modification in E. coli have emerged recently from the laboratory of George Church, these are a long way from genomes designed and constructed to perform unique metabolic activities.

The tools and techniques developed by my team to assemble a completely synthetic bacterial genome, while relatively efficient (we built the entire 1.1-million-base-pair synthetic genome in less than one month), are also still quite expensive ($0.30 per base pair) due to the current cost of oligonucleotide synthesis. Fortunately, this work has helped create a demand for rapid, accurate, cheap DNA synthesis, which has led to some very novel approaches that could help reduce these costs. Over the past 23 years, the cost of DNA sequencing has dropped 8 orders of magnitude. Similar improvements with DNA synthesis await technological breakthroughs that are tantalizingly close.