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Rewriting Life

Chromosome Cure

Every human cell carries 46 chromosomes, the DNA-and-protein packages that transmit genes from generation to generation as cells divide. Lately, scientists have been wondering whether they can fool the machinery of the cell by inserting a synthetic 47th chromosome furnished with genes of their own choosing. Two companies, Athersys in Cleveland, OH, and Chromos Molecular Systems in Burnaby, British Columbia, are beginning to find an answer; they are testing artificial chromosomes as a safe and effective way to introduce therapeutic genes into patients suffering from deadly genetic disorders.

Their hope is that the fake chromosomes will provide a viable alternative to conventional gene therapy, which typically uses viruses to deliver gene replacements in treatment of such diseases as hemophilia and cystic fibrosis. The small size of the viruses limits the number of genes that can be delivered, and because the viral proteins can also cause dangerous immune reactions, the strategy is risky. Artificial chromosomes might spare gene therapy patients from these problems. An artificial chromosome can carry any number of genes, is ignored by the immune system, and functions independently of other chromosomes, so the technique “represents potentially a response or an answer to those challenges,” says Huntington F. Willard, director of the Duke University Institute for Genome Sciences and Policy. Willard and Athersys researchers created the first human artificial chromosomes five years ago.

Now Athersys and Chromos are trying to prove Willard right. In experiments on mice, Chromos has demonstrated that the bogus chromosomes are transmitted from mother cells to daughter cells during cell division and from one generation to the next as animals reproduce. More recently, Chromos scientists proved that they can raise red blood cell counts in mice by injecting cells that contain artificial chromosomes bearing the gene for erythropoeitin, a protein that stimulates blood cell production. If similar constructs work in humans, the company’s potential targets include diabetes, hemophilia, and various metabolic disorders.

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Willard anticipates that human trials are a year or more in the future. But skeptics abound. Michle Calos, a Stanford University geneticist who previously had worked with artificial chromosomes, has since shifted her focus to other gene-therapy methods such as inserting therapeutic genes at specific places on natural chromosomes. Says Calos, “I’m not sure that that approach will make it to the clinic, because I think there might be alternatives that are just more competitive.”

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