Researchers at Glasgow University have invented protein machines that will allow us to edit the messages encoded in our DNA.

The bases of the DNA double helix spell out the text of Life. And, just as with more ordinary documents, we sometimes think that the text could be improved upon. Most people will be familiar with the potential benefits as well as the controversy of deliberately changing the DNA text of living organisms, in the shape of gene therapy or GM (genetically modified) crop plants. Nature, of course, has always been editing DNA; its way of 'cutting and pasting' is called site-specific recombination.

Specialised recombinase enzymes cut the DNA precisely at sites (bits of DNA sequence that they recognise and to which they bind), then paste the ends together to make new arrangements. For example, they can delete a section of DNA between two sites or insert a new 'paragraph' into the DNA text.

Scientists would like to harness the abilities of these recombinases for their own purposes, but are currently restricted in what they can do because the recombinases are extremely fussy about the sites they will use. In an ideal world, scientists would be able to choose any stretch of DNA sequence, and make a recombinase that cuts at precise positions within it.

The research carried out by Professor Marshall Stark's group at the University of Glasgow (Institute of Biomedical and Life Sciences) recently published in Proceedings of the National Academy of Sciences of the USA is a big step towards this ideal world. Stark's research group works on recombinases from transposons - little chunks of 'selfish DNA' that can jump about between different sequences in a cell.

The authors have made a two-part enzyme, with a cut-and-paste module from a transposon recombinase attached to a 'zinc finger' DNA recognition module from a mouse protein. This hybrid enzyme promotes recombination at new sites that are specifically recognised by the zinc finger module.

The zinc finger module can be adapted to recognise almost any short DNA sequence, so it should soon be possible to make variations on this theme, 'designer recombinases', that cut and paste natural sequences in the genomes of important organisms such as humans or plants.

Possible uses of these designer recombinases are almost limitless; for example, we may be able to cut out a faulty gene that causes a human disease, or alter a plant's DNA sequence without leaving any foreign DNA in the cells.

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Dr. Marshall Stark, Institute of Biomedical & life Sciences, Tel. 0141-330-5116

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First published: 15 July 2003