用RNAi技术治疗退行性神经疾病
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Gene therapy could ease the symptoms of some devastating brain disorders, according to evidence presented to US conference last week.Many neurodegenerative diseases are caused when the brain makes mutant proteins that build up in the brain, causing gradually worsening symptoms. These brain-wasting diseases are devastating and incurable. They include Huntington’s disease, which affects around 250,000 people in the United States.
Beverley Davidson of the University of Iowa in Iowa City and her colleagues hope that gene therapy will help treat such diseases. The approach involves trying to correct genetic abnormalities by injecting an animal or person with corrective sequences of DNA or RNA.
The researchers tested their therapy in mice with a disorder that mimics a disease called spinocerebellar ataxia type 1, which leaves sufferers progressively less able to walk.
The therapy eliminated pockets of damaged brain tissue from the mice and corrected the physical symptoms of the disease.
This is the first time that gene therapy has been shown to cure a disease like spinocerebellar ataxia. But the finding is also significant because it is the first time that gene therapy has been used to cure a so-called dominant progressive brain disorder. Such diseases occur in cases where a patient inherits a defective copy of a gene from just one parent.
Most gene therapy involves replacing a missing gene sequence. But in dominant disorders it is the mutant sequence itself that causes the problem, so any therapy needs to actively block a sequence rather than just replacing one.
To do this in the mice, Davidson’s team used a technique called RNA interference. The researchers isolated pieces of genetic material that bind to and block the mutant gene. They packaged these into stripped-down virus particles and injected them into the mice. The virus used was an adeno-associated virus that does not cause disease in mice or people.
After the injections, the proteins created by the mutant gene disappeared and the mice seemed to improve, the researchers told the annual meeting of the American Society of Gene Therapy in Minneapolis, Minnesota last week.
Davidson and her co-workers also reported at the meeting that RNA interference stopped human cells in culture dishes from producing the mutant proteins found in Huntington’s disease. For this work, they used a different virus to deliver the RNA to cells. The virus is similar to human immunodeficiency virus (HIV), but infects cats. The team took out all the infectious parts of the virus and replaced them with the pieces of therapeutic RNA.
Davidson says she hopes that her technique will move quickly into clinical trials. “The data are very promising; we hope we will be able to use RNA interference as a therapy for dominant neurodegenerative diseases.”
http://www.nature.com/nsu/040607/040607-3.html
http://sciencenow.sciencemag.org/cgi/content/full/2004/607/1
