IT鈥橲 ONE thing to use jumping genes from flies to make transgenic animals (see opposite), but quite another when it comes to gene therapy in people. The idea of having a bit of fruit fly DNA inserted into your cells is uncomfortably reminiscent of the movie The Fly.
In principle, the added DNA should consist only of the desired genes flanked by short marker sequences鈥攕o you wouldn鈥檛 have much fly in you. But this DNAis inserted randomly. One fear is that it could land in the wrong place, knocking out vital genes and making cells cancerous.
The chances of that are minuscule, says Perry Hackett of the University of Minnesota. Only about 1.5 per cent of our DNA consists of genes, we have two copies of most of them and cells usually commit suicide if they have a serious defect. In all the gene therapy experiments that have been carried out, there鈥檚 never been any evidence of such problems, he says.
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A more realistic worry, if Tosk鈥檚 method is as good as the company claims, is integration of a gene into the human germline. If the extra gene ends up in a patient鈥檚 sperm or egg cells, it could be passed on to any children that person has.
Regulatory agencies such as the US Food and Drug Administration do not allow any gene therapy trials that might result in germline alteration. To minimise the chances of this, Tosk鈥檚 Patrick Fogarty says it should be possible to target organs where the gene is needed, such as the heart or lungs.
But it might not be that easy. Even the relatively inefficient viruses already used in gene therapy occasionally seem to find their way into gonads (快猫短视频, 14 March 1998, p 7). In 2000, the American Association for the Advancement of Science concluded that it is 鈥渧ery likely鈥� that some gene therapy trials authorised in the US have already had unintentional impacts on the germline.
Some argue that germline transmission is desirable, though. A person with a genetic disease might welcome a cure that also protects their future children. 鈥淧ersonally I think gene therapy without a germline component is unethical,鈥� Fogarty says. 鈥淗owever, I wouldn鈥檛 want any of the current viral technologies used in the human germline.鈥�
The effects of random integration are more of a worry if the germline is affected. A relatively minor mutation could have serious consequences if it were present in all a person鈥檚 cells. Fogarty says, however, that Tosk is working on a way to get its transposons to insert genes into particular sites in the genome. If the company really can deliver an efficient way of targeting genes, it could undermine many of the current arguments against germline gene therapy.