Researchers can now inexpensively program the chemical synthesis of entire genes on a single microchip

Devices the size of a pager now have greater capabilities than computers that once occupied an entire room. Similar advances are being made in the emerging field of synthetic biology at the University of Houston, now allowing researchers to inexpensively program the chemical synthesis of entire genes on a single microchip.

Xiaolian Gao, a professor in the department of biology and biochemistry at UH, works at the leading edge of this field. Her recent findings on how to mass produce multiple genes on a single chip are described in a paper titled "Accurate multiplex gene synthesis from programmable DNA microchips," appearing in the current issue of Nature, the weekly scientific journal for biological and physical sciences research.

"Synthetic genes are like a box of Lego building blocks," Gao said. "Their organization is very complex, even in simple organisms. By making programmed synthesis of genes economical, we can provide more efficient tools to aid the efforts of researchers to understand the molecular mechanisms that regulate biological systems. There are many potential biochemical and biomedical applications."

Most immediately, examples include understanding the regulation of gene function. Down the road, these efforts will improve health care, medicine and the environment at a fundamental level.

Using current methods, programmed synthesis of a typical gene costs thousands of dollars. Thus, the prospect of creating the most primitive of living organisms, which requires synthesis of several thousand genes, would be prohibitive, costing millions of dollars and years of time. The system developed by Gao and her partners employs digital technology similar to that used in making computer chips and thereby reduces cost and time factors drastically. Gao's group estimates that the new technology will be about one hundred times more cost- and time-efficient than current technologies.

With this discovery, Gao and her colleagues have developed a technology with the potential to make complete functioning organisms that can produce energy, neutralize toxins and make drugs and artificial genes that could eventually be used in gene therapy procedures. Gene therapy is a promising approach to the treatment of genetic disorders, debilitating neurological diseases such as Parkinson's and endocrine disorders such as diabetes. This technology may therefore yield profound benefits for human health and quality of life.

"The technology developed by Dr. Gao and her collaborators has the potential to make research that many of us could only dream about both plausible and cost effective," said Stuart Dryer, chair of the department of biology and biochemistry at UH. "In my own research on neurological diseases, we've often wished we could rapidly synthesize many variations of large naturally occurring genes. The costs of current technology have prevented us from doing this, but Dr. Gao's research will break down that barrier."

This technology offers tremendous potential benefits, as synthetic genes could allow for development and production of safer, less toxic proteins that are currently used in disease treatment. It also could allow for production of large molecules that do not occur naturally, but that are needed for new generations of vaccines and therapeutic agents, including vaccines for HIV and other viral diseases. This technology also will facilitate development of new medications through the creation of humanized yet synthetic antibodies that could be especially useful in detection and treatment of infectious organisms that could be used by terrorists.

Gao's co-authors include Erdogan Gulari and Xiaochuan Zhou from the University of Michigan and George Church of Harvard University. Gao, Gulari and Zhou are partners in Atactic Technologies, a company that produces and markets products for life sciences research. Atactic Technologies currently holds the license to this breakthrough technology, called picoarray gene synthesis. UH and the University of Michigan are co-holders of the patents to these DNA microchip technologies.

Prior to coming to UH in 1992, Gao was a senior investigator at Glaxo Research Laboratory and received her postdoctoral training at Columbia University, her doctorate from Rutgers University and bachelor of science from the Beijing Institute of Chemical Technology. She is an expert in nucleic acid chemistry, biomolecular nuclear magnetic resonance technology, structural biological chemistry and combinatorial chemistry. Research in her lab involves the interface of chemistry and biological sciences. Holding patents in biochip technologies, her current focus is to understand the relationships of function and structure of complex genomes of humans and other species. Gao's research has been funded by the National Institutes of Health, the Welsh Foundation, the Texas Higher Education Coordinating Board, the National Foundation for Cancer Research, the Merck Genomic Research Institute and the Defense Advanced Research Projects Agency.