Southampton and Oxford chemists to develop cheaper DNA building system

23 February 2012

A team of chemists from the Universities of Southampton and Oxford have been awarded over £4 million to develop a new technique for building DNA and RNA segments together.

Their project, which is being funded by a strategic Longer and Larger (sLoLa) grant from the UK Biotechnology and Biological Sciences Research Council (BBSRC), could make biotechnology research cheaper and more efficient.

The scientists hope that their research could enable the production of useful DNA and RNA molecular structures more efficiently and on a larger scale than is possible using current enzyme-based technologies. The project could also lead to the creation of previously unimaginable molecular machines with new industrial and medical uses.

Professor Tom Brown of the University of Southampton, who will jointly lead the project, commented: “At the moment, synthesising long DNA molecules by chemical methods is slow and requires a great deal of skill. To avoid this, biologists usually ask chemists to make a large number of very short DNA strands which they glue together using enzymes. These enzymes, which have evolved to work under very specific conditions, work brilliantly if you treat them kindly.

“However, they are delicate, temperamental, and refuse to work with heavily modified DNA or RNA. We have found that we can ‘click’ DNA and RNA segments together using chemical methods that can replace the enzymes. These chemical linkages are stronger and less choosy than enzymes and can be produced in large amounts for industrial scale applications.”

The ability to ‘click’ DNA together opens up the possibility of producing new DNA structures decorated with a variety of useful chemical modifications for industrial uses in the Bioeconomy, including in clinical applications. However the ‘click’ method has not had the luxury of millions of years of evolution, and it inserts an unusual linkage into DNA. Importantly though, the researchers have recently demonstrated that a bacterial cell can copy and read a strand of DNA that has been ‘clicked’ together, and enzymes can also use it to make RNA. It seems that cells don’t notice the unusual ‘click’ linkages and so process the click-linked DNA normally.

Scientists are currently exploring whether we can use DNA to treat a whole range of diseases including certain cancers and HIV. We know that people who possess certain genes are more susceptible to these diseases so if we can turn off the appropriate gene we might be able to help combat the disease. One of the problems holding back this approach is that long strands of DNA are more effective at turning off genes than shorter ones, but are less readily taken up by the cells in our bodies. Using ‘click’ chemistry it might be possible to send in a series of short strands which then self-assemble in the cell and turn off the disease gene.

“We’re really excited by the possibilities that this project could open up” said Professor Douglas Kell, Chief Executive of BBSRC. “The ‘click’ technique could make DNA production cheaper, quicker and more efficient and deliver a range of useful new clinical and commercial molecules. However, we also need to be aware of the implications of making DNA assembly more widespread and accessible.

“BBSRC ran a public dialogue in 2010 on ‘synthetic biology’ which encompassed new technologies like these. The dialogue aimed to gauge people’s hopes and fears for these new technologies to make sure that we, and the scientists engaged in this research, don’t lose sight of the social and ethical dimensions of their work. This research clearly has the capacity to do great good but must be done thoughtfully with an eye on the wider implications. ”


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