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Published online:
10 November 2004; | doi:10.1038/news041108-11
RNA treatment lowers cholesterol
Erika Check
Mouse study points way for targeting
'interference' therapies.
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Nature |
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Cholesterol
levels have been lowered in mice by using tiny pieces of genetic
material to block a particular gene. The demonstration shows that the
experimental technique, called RNA interference (or RNAi), could be a
practical way of curing a wide range of diseases.
RNAi
works by using small molecules of RNA to trigger a cell to shut off a
particular gene, for example, one that codes for a harmful protein.
Clinical trials that use RNAi to treat an eye disease called macular
degeneration have already begun.
But
scientists have had a hard time finding a convenient way to deliver the
treatment to patients so that it reaches the right part of the body. In
the macular degeneration trials, for example, scientists inject the
treatment directly into the eye.
Researchers
from the biotechnology company Alnylam, based in Kulmbach, Germany, and
Cambridge, Massachusetts, have figured out a way to solve the problem,
at least for treating high cholesterol. They modified the RNA molecule
used to trigger the interference by attaching a cholesterol molecule to
it.
 This
is a fairly simple solution to a problem that could have been immense
in this field.  |
John Rossi
Beckman
Research Institute of the City of Hope in Duarte, California |
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Cells
that make cholesterol have cholesterol receptors on their surface, so
that they can sense levels of the molecule in the blood. Adding the
cholesterol molecule to the RNA ensures that the complex is taken up
specifically by these cells, in the liver and small intestine.
When
the researchers injected this modified molecule into mice, they found
that it cut the animals' levels of 'bad' cholesterol by 44%. They
report their results in this week's Nature1.
Simple solution
Another
concern about RNAi has been whether the therapy might affect genes
other than the ones targeted, causing side-effects. The researchers
checked the activity of a few genes unrelated to their target gene, and
found that they were not affected.
The
company is excited about the result. "We view our work as a historic
step forward in the development of RNAi therapeutics as a potential new
class of drugs," says John Maraganore, head of Alnylam.
He
says the company aims to develop similar methods to treat other sorts
of diseases, such as diabetes, obesity and cancer. "There are clearly
many diseases of interest here," he says.
Other
researchers agree that the new method has removed a major roadblock
that could have prevented RNAi from moving to the clinic.
"This
is a fairly simple solution to a problem that could have been immense
in this field," says John Rossi, a molecular biologist at the Beckman
Research Institute of the City of Hope in Duarte, California.
But
he points out that Alnylam still needs to overcome many practical
issues before its research in mice can be translated into patients. The
doses used in the mice were quite high, and would be costly and
impractical to give to people. And it's not clear how often a person
would need to be injected with the treatment, or whether it could be
delivered in some other form.
Alnylam
says it is working on these issues, and hopes to design more effective
molecules that could be used in smaller doses in the future. In the
meantime, it will file a clinical trial plan with the Food and Drug
Administration next year, which will use RNAi to treat an eye disease.
If its plan is approved, Alnylam will be the third company so far to
ask the federal agency to approve an RNAi therapy.
References
- Soutschek J., et al.
Nature, 432. 173 - 177
(2004). | Article |
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