Genetics researchers have invented a whole new class of drugs aimed at a recently-discovered set of genes. As this ScienCentral News video explains, these genes are likely behind many common diseases including cancer, diabetes and viral infections.
Drugs for Your Genes
Researchers working with mice report that a new kind of drug can stop many genes in the liver that produce cholesterol.
"By switching off specific genes that are responsible for making cholesterol in our bodies we are able to reduce cholesterol levels in the blood using these novel drugs," explains geneticist Markus Stoffel. "These drugs have the remarkable property of being very specific, long-lasting, and they show no side effects."
The new drugs, invented by Stoffel and his research team at Rockefeller University, in collaboration with Alnylam Pharmaceuticals, work by shutting down a recently-discovered type of gene called a micro RNA. Each micro RNA can control many other genes in our bodies, including many disease genes. While scientists suspect that some micro RNA's play a role in causing cancers and viral infections, most of their functions are still a mystery. To study them, the researchers wanted a way to switch off specific micro RNA's in living animals in order to find which genes each controls. They designed molecules they call "antagomirs" that can match up with a specific micro RNA and block, or "silence" it.
"We recognized that the micro RNA's have a specific sequence, a specific order of bases, and we could design molecules, drugs, that are complementary, that block in a one-to-one fashion that specific sequence of the micro RNA's," says John Maraganore, CEO and President of Alnylam, "and therefore are able to shut down, or stop, these micro RNA's from doing what they do." A unique antagomir can be designed to silence each specific micro RNA.
As they wrote in the journal Nature, they injected these drugs into the bloodstream of mice "and noticed that after a very short period of time, they were able to completely inactivate the micro RNA's they were targeting," Stoffel says.
While testing an antagomir specifically targeted at a micro RNA found in high levels in the liver, they noticed that the mice's blood cholesterol level dropped. "We were able to reduce the levels of this micro RNA to basically to zero. As a result," says Stoffel, "we noted a 40-percent reduction in cholesterol levels in the blood of these animals." Stoffel says they noticed no toxicity or side effects in the mice, which he attributes to the drug's specificity.
He says the new drugs will not only be a powerful research tool, but could one day be drugs for people, hopefully allowing doctors to treat diseases "much more specifically than they have in the past... There are many diseases, such as cancer, metabolic diseases and infectious diseases where genes have increased activity," he explains. "By regulating micro RNA's with anatagomirs we are hoping to regulate these disease-causing genes," he says.
"Our next steps are really beginning to expand this work into designing drugs toward other micro RNA's that could allow us to target cancer, to target viral infection, first in animal models… but then ultimately in human trials," says Alnylam's Maraganore.
In the meantime scientists will be able to use the new drugs to study the functions of all the micro RNA's found in the body. They estimate there are some 250 to 300 micro RNA's in the human genome. "Once we find out the function of all these… more than 250 micro RNA's and their role in disease processes such as cancer, infectious diseases and metabolic diseases, we'll be able to specifically reduce the activity of micro RNA's that have increased expression in these diseases," says Stoffel.