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5 December 2013 11:26 am ,
Vol. 342 ,
An animal rights group known as the Nonhuman Rights Project filed lawsuits in three New York courts this week in an...
Researchers have been hot on the trail of the elusive Denisovans, a type of ancient human known only by their DNA and...
Thousands of scientists in the Russian Academy of Sciences (RAS) are about to lose their jobs as a result of the...
Dyslexia, a learning disability that hinders reading, hasn't been associated with deficits in vision, hearing, or...
Exotic, elusive, and dangerous, snakes have fascinated humankind for millennia. They can be hard to find, yet their...
Researchers have sequenced and analyzed the first two snake genomes, which represent two evolutionary extremes. The...
Snake venoms are remarkably complex mixtures that can stun or kill prey within minutes. But more and more researchers...
At age 30, Dutch biologist Freek Vonk has built up a respectable career as a snake scientist. But in his home country,...
- 5 December 2013 11:26 am , Vol. 342 , #6163
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Helping Liver Cells Heal Themselves
11 November 1998 7:30 pm
Researchers have come up with a new cut-and-paste technique that corrects tiny errors in a gene that makes a crucial liver enzyme in rats. The findings, presented this week at the annual meeting of the American Association for the Study of Liver Diseases in Chicago, may usher in a new breed of gene therapy that could potentially cure diseases, such as hemophilia and sickle cell anemia, that are caused by mutations in a single nucleotide base.
Traditional forms of gene therapy have relied on retrofitted viruses to shuttle entire sequences of corrective genes into patients' cells--a difficult task. To trick the cells into fixing their own genes, the researchers--hepatologist and cell biologist Clifford Steer and biochemist Betsy Kren of the University of Minnesota, Minneapolis, and their colleagues--turned to artificial dumbbell-shaped pieces of DNA and RNA called chimeric oligonucleotides. These pieces faithfully match the genetic sequence of a mutated gene except for the corrected version of the wrong nucleotide. The investigators bypassed a viral shuttle by bundling the oligonucleotides inside coats of oil-like molecules or tacking them onto polymers designed to bind to specific liver cells.
The team tested the modified oligonucleotides in rats that carry a single-nucleotide defect in an essential liver gene known as UDP-glucuronosyltransferase-1. Humans with the faulty gene are afflicted with Crigler-Najjar disease, a fatal illness in which patients cannot break down or excrete bilirubin and end up severely jaundiced. After five daily injections of the oligonucleotides into the tail veins of 20 rats, all had converted up to 25% of their defective liver genes to normal versions. (Most gene therapy experiments consider a 1% to 2% conversion rate a success.) "It's as though the cells never knew they had the mutant sequence," says Steer, the lead investigator. Bilirubin levels dropped by greater than half and have stayed there for 6 months so far.
"This is exactly what I have been waiting for," says Michael Blaese, who is so enamored with the technique that he is leaving his post as chief of the clinical gene therapy branch at the National Human Genome Research Institute in Bethesda, Maryland, to work for the company that manufactures the novel RNA/DNA oligonucleotides. "The potential, if real, is incredible," says Mario Capecchi, a longtime gene therapy researcher at the University of Utah, Salt Lake City. "But I'd be much more excited if others are able to reproduce [the finding]."