Gene guns: How one researcher improved his shot

17th January 2007

How do you refine a large-scale tool to create a precision instrument capable of firing DNA into a single cell? That is the challenge research assistant John O’Brien faced when he was first presented with a gene gun at the MRC’s Laboratory of Molecular Biology (LMB) in 1998. He cracked it, though his inspiration came not from the gene gun itself but from a retired policeman’s description of machinegun mechanics.

A gene gun is a tool scientists use to insert genetic information like DNA or RNA into a cell. It is hand held and roughly the size of a hair dryer. It was originally developed to create new strains of plants. Powered by a pulse of helium gas, it pushes its genetic bullet easily through the cell membrane and into the heart of the cell where it inserts itself into the cell’s own genetic machinery.

‘‘From the beginning I knew I had to improve the gene gun’s accuracy.’’ O’Brien explains, ‘‘with the original model, trying to insert material into the cells was like shooting a clay pigeon with a sawn off twelve bore shotgun - you don’t just hit the target but everything around it in the process. To improve accuracy I worked on reducing gas pressure, which in turn cut down on tissue damage.’’

‘‘It was the policeman’s explanation of the angle of holes in the barrel of a German machinegun that gave me the breakthrough I needed. In the modified gene gun the holes allow the helium gas to escape, this then reduces the recoil that causes tissue damage. I experimented until I found the optimum angle for minimal tissue damage.’’
This improved accuracy also increased penetration, so now the gene gun can be used to insert DNA into smaller targets and deeper tissues. O’Brien recently published a protocol in the journal Nature Protocols, detailing how the improved gene gun can be used to label single brain cells with dye. This process is known as diolistic labelling and allows scientists to view interactions between living brain cells by observing the movement of the dye.

This method of imaging has allowed scientists to pick out cell features from within crowded layers of living tissue. It has already been used to track cells as they move around, examine growth and determine the exact shapes of dendrites, the cells on the tip of neurones that transmit and receive signals in the brain.

O’Brien’s efforts to refine the gene gun are likely to make it a useful clinical tool in the future, he predicts:

‘‘The version of the gene gun I use in research at the moment isn’t what we would use to give people vaccines, but a further modified design could eventually be used to deliver DNA vaccines into human skin or muscle without causing tissue damage, it could also be used long-term in gene therapy. Whether this will be successful will depend on the outcome of clinical trials and careful investigation, but I’m confident that the gene gun will be valuable both as a research and as a clinical tool in the long-term.’’
‘Diolistic labelling of neuronal cultures and intact tissue using a hand-held gene gun’ was published in Nature Protocols in November 2006. Vol.1.No.3 pg1517.

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