IT TOOK more than a decade for the Human Genome Project to sequence the 24 different human chromosomes, but already other researchers are preparing to take another huge step. They have shown it is possible make artificial chromosomes that can pass from one generation to the next.
Such techniques might soon make it possible to treat patients by loading their cells with extra chromosomes that are purpose-built to produce a therapeutic protein and operate entirely independently of our natural chromosomes. It might even be possible to treat genetic diseases with extra chromosomes that can themselves be inherited, though this would mean challenging the taboo against "germline" gene therapy.
The ground has been laid in experiments on animals at a Canadian biotechnology company. A new paper by Deborah Co and her colleagues at Chromos Molecular Systems in Burnaby, British Columbia, describes for the first time a mouse that passed such a chromosome through three generations of descendants, apparently without any harm to the animals.
Co's experiments show that each generation of mice carried the new chromosome, and that it was active. It served as a carrier for the gene that makes beta galactosidase, a marker protein that turns blue on exposure to a chemical.
The researchers started with a natural chromosome gutted of all its functional genes but retaining other key elements (New Scientist, 23 October 1999, p 4). These include the telomeres at the tips of chromosomes, which protect them from fraying and recombining; the central, X-shaped centromere, which orchestrates duplication during cell division; and regions of satellite DNA at the root of each of the chromosome's four arms, made up of "junk" genetic material bereft of working genes.
Co and her colleagues at Chromos have developed a way to implant genes into the satellite DNA. They can implant multiple copies of the same gene, and implant genes far larger than is possible in any other "gene shuttle" technique for ferrying DNA into cells. Once modified, the artificial chromosome can be duplicated hundreds of thousands of times. The company says that the amount of protein produced rises in step with the number of gene copies, and that the chromosome does not interfere with natural chromosomes and so should be safer than inserting genes into host DNA.
Because the company is about to sell shares on the Canadian stock market, it is barred from talking to the media. But in a prospectus available to the public, Chromos says it plans to insert the chromosomes into cells which will be grown in fermenters to produce beneficial proteins and to genetically engineer animals so that they produce valuable proteins in their milk. It has already produced a second line of mice, this time carrying a gene that makes a therapeutic antibody.
In a project with the Academic Medical Center at the University of Amsterdam, Chromos is testing artificial chromosomes which produces a protein to ease the symptoms of rheumatoid arthritis. The team inserts the chromosome into the cultured cells of a rat with arthritis and then injects them into the rat's joints. If the system works in rats, then trials could begin in people.
Author: Andy Coghlan
New Scientist issue: 8th July 2000
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