Researchers devise cheaper way to make genes

Harvard researchers have devised a way to greatly decrease the cost of making artificial genes in the laboratory, an advance that could increase the ability of geneticists to explore and test new theories about the building blocks of life.

Harvard Genetics Professor George Church said that after years of technological advances, gene synthesis – or making artificial genes – was one of the few things not automated in the laboratory.

Gene synthesis is a critical process that allows researchers to test new theories, for example, by making genes that create specific proteins with novel properties of interest to scientists.

Church, in research published in December in the journal Nature, described a new way of making genes that is very accurate and that can reduce the cost of making letters of genetic code from about nine letters for a dollar to as many as 20,000 for a dollar.

Church and colleagues made short pieces of DNA called oligonucleotides. Instead of making the oligonucleotides in separate vessels as is done now, the research uses gene chips to create them. Church and colleagues washed them from the chip into a solution, where they were multiplied using a process called polymerase chain reaction.

After multiplying the bits of DNA about a millionfold, Church and colleagues added a step to find DNA strands that don’t contain errors, by using a second set of oligonucleotides that would attach to the new ones and melt at a lower temperature if errors were present.

Church’s research was conducted with Harvard colleagues Jingdong Tian and Hui Gong, as well as with Nijing Sheng and Xiaolian Gao of the University of Houston, Xiaochuan Zhou of Atactic Technologies Inc., and Erdogan Gulara of the University of Michigan.

To test the method, Church and colleagues assembled 21 genes of the E. coli bacteria that create a particle inside the cell that is important in creating proteins, called a ribosome.

alvin_powell@harvard.edu