Synthetic Genomics: Microfactories Made to Order

September 2009
Topics: Genetics, Genetic Engineering, Biotechnology
Using synthetic genomics, genetic engineers can build from scratch cells capable of producing new substances, such as biofuels or medicines, or performing new functions, like countering terrorist bioweapons.
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Custom-made DNA

In traditional genetic engineering, the genetic material of living cells is altered in order to make the cells capable of producing new substances or performing new functions. In synthetic genomics—a field of genetic engineering—naturally occurring genetic material is not used as a starting point. Instead, synthetic genomics makes use of chemically synthesized, customdesigned, commercially produced segments of DNA to reprogram cells.

The emergence of this field is driven by recent advances in the underlying technology of commercial DNA synthesis that allow biologists to produce and assemble segments of DNA quickly and cheaply with almost perfect accuracy. While the synthesis of small segments of DNA has been possible for two decades, the use of these early techniques to produce a genome (the complete blueprint, in the form of DNA, for the construction of an organism) would have required years of work and been prohibitively expensive. DNA production and assembly techniques have advanced to the point that a medium-sized virus can now be constructed in weeks. In addition, these improvements have led to a rapid increase in the number of companies that offer whole gene synthesis. The resulting competition has lowered prices to within the budgets of most researchers.

What a Designed Genome Can Do for You

Synthetic genomics is already being incorporated into the production of conventional chemical products such as colorants, solvents, plastics, vitamins, food additives, pesticides, and alcohols. Among other benefits, synthetic genomics technologies are proving to be cheaper, more environmentally friendly, and more efficient than traditional chemical synthesis methods.

In the long term, however, the greatest impact of synthetic genomics is likely to be in the production of high-value chemical products. "Genome engineers" have recently demonstrated the ability to develop cell-based factories that significantly improve on the traditional production methods of certain chemical compounds. By eliminating steps in the natural biosynthetic process, stunning increases in efficiency are possible. For example, the Bill and Melinda Gates Foundation is funding a team of researchers from the Berkeley Lab; the University of California, Berkeley; the California Institute of Quantitative Biomedical Research; and Amyris Biotechnologies that is using synthetic genomics to produce the anti-malarial drug artemisinin at 1/10th the cost of extracting the drug from natural sources. Research is currently underway to engineer cell-based production for many other high-value chemicals.

Another significant application of synthetic genomics could be the cost-effective production of biofuels. Recent efforts in this area include attempting to engineer a single organism capable of producing ethanol or butanol from biomass. While synthetic genomics is not the only method capable of producing the enzymes needed for this process, it's among the most promising. If successful, synthetic genomics techniques might be able to produce ethanol at a cost competitive with gasoline. In addition, synthetic genomics has the potential to supply fundamentally new production techniques for other green energy sources such as hydrogen.

Building biological systems capable of producing such tailored products depends on the ability to design, model, simulate, and debug cellular components and processes. MITRE is developing a tool, called the Protein Design Pipeline, that integrates in a seamless manner all of the previously mentioned computational modules. Running on a high-performance computing system, the Protein Design Pipeline can screen millions of potential receptor structures and identify those that will bind to a compound of interest with high affinity. The first group of detector proteins made using this tool is currently being tested in the MITRE biotechnology laboratory. MITRE also hopes to apply the Protein Design Pipeline to create countermeasures against existing chemical nerve agents.

What a Designed Genome Can Do to You

Such countermeasures are unfortunately necessary: The potential abuse of synthetic genomics by terrorist organizations or rogue nations is a serious concern. The same techniques used to produce anti-malarial medicine could also produce pandemic influenza and smallpox. The Biological and Toxin Weapons Convention proscribes the development, acquisition, or production of biological agents as weapons, whether produced by synthetic genomics or any other means.

While synthetic genomics is not the only way to construct a biological warfare agent, what it does allow for is faster, cheaper, and more accurate production of such agents. Based on current technology, it is believed that constructing an infectious virus via synthetic genomics will continue to be more difficult than obtaining it from a natural source or laboratory stock in the near term. However, if synthetic genomics technology continues to develop at its current pace, this may not be the case ten years from now. At that point, it may be easier for a nefarious actor to order a viral genome (whole or in parts) from commercial sources than to obtain it from nature.

To limit the ability to order dangerous genomes from commercial sources would require tools that can check DNA synthesis orders for suspect sequences. MITRE has developed a prototype of just such a tool: the DNA Order Tracking System. Initial tests have shown that the system is able to identify suspect sequences from a pool of hypothetical orders. MITRE is currently focusing on improving the scaling and speed of the system, as well as locating any gaps in the system's identification spectrum.

Realizing a Vision

The continued maturation of synthetic genomics will lead to a future where a researcher could design a genome that performs a specific function, electronically submit that sequence to a DNA synthesis company, and receive the physical genome by overnight delivery. MITRE will continue to work toward the realization of this vision by researching and developing the necessary biological modeling and fabrication tools, while at the same time brainstorming the countermeasures necessary to prevent terrorists from exploiting these same tools.

——by John Dileo

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