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Thursday, October 21, 1999 Published at 09:26 GMT 10:26 UK


Major step forward for gene therapy

In humans, 46 chromosomes are arranged in pairs

Canadian scientists have succeeded in putting an artificial, extra chromosome into mice that is passed to their offspring.

The development, reported at a London conference this week, is a significant development in the on-going efforts to find more effective ways of introducing new genes into humans and animals.

Current methods of incorporating genes, such as simply injecting them into cells, is highly inefficient and risky. Introducing a whole chromosome - the structure used by cells to bundle up DNA - could be a more successful solution.

And it also raises the prospect that germline gene therapy in humans - making genetic changes that are inherited by future generations - will one day be technically feasible. However, the team behind this latest development stress that they will not be using their technology, or allow anyone else to use it, for this purpose.

At the moment, geneticists wanting to make major genetic modifications to an animal - to create a transgenic animal - inject genes into newly-fertilised embryos. It is a problematic process because the genes are not always taken up by the embryo's genome. And even when they are, the genes can be spliced into chromosomes where they will have no effect or, worse still, where they can disrupt other genes.

Millions of laboratory animals are "wasted" each year in this process and are destroyed. Whilst society might accept this in animals, it would be an intolerable way to introduce genetic changes into humans.

A 'first' in mammals

What Chromos Molecular Systems Inc of Burnaby, British Columbia, have done is to "build" an artificial chromosome, with the new DNA already spliced in, and introduce the whole structure into the developing embryos.

By attaching a fluorescent dye to the chromosomes, they were able to confirm that the mice could subsequently pass the "gene packets" on to their offspring. "It's the first time an artificial chromosome has ever been shown to be inherited in any mammal," Eileen Utterson, vice-president of corporate development for Chromos, told New Scientist magazine. "Because the artificial chromosome is separate, it doesn't interfere with the cell's own genetic machinery."

The company plans to use the technology to create herds of genetically-modified (GM) animals which will express useful drug compounds in their milk.

It may also have a significant advantage over current methods used in conventional, non-germline gene therapy in humans. In these treatments, scientists try to add therapeutic genes to the cells of specific tissues in adult or child patients.

The intention is to counter the genetic mutations which give rise to diseases like cause cystic fibrosis. But none of the techniques employed are very successful.

Using an artificial chromosome to ferry the DNA into a cell may prove more fruitful. It would also allow much larger quantities of genetic material to be introduced than is currently possible.

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