Scientists have used a genetic technique to cut cholesterol in mice in a groundbreaking way which could one day be used to treat a range of human illnesses.
Researchers at U.S.-based Alnylam Pharmaceuticals Inc blocked the action of a gene involved in cholesterol metabolism by using RNA interference (RNAi).
“Alnylam’s progress really shows the ability of using RNA interference to silence disease-causing genes in a manner that has not been previously available,” John Maraganore, chief executive officer of the company, said in a telephone interview.
RNAi is a mechanism that occurs naturally in cells to regulate or silence specific genes. Many diseases develop when genes do not work properly so RNAi offers tremendous potential to create a new generation of selective drugs against harmful genes.
“The key technical challenge for achieving the promise of RNAi is overcoming the hurdle of delivery. This is precisely the hurdle addressed by our findings today,” said Maraganore.
In research reported in the science journal Nature, Hans-Peter Vornlocher and his colleagues at the company synthesized molecules called siRNA to target the gene and trigger RNAi in cells.
They also attached a cholesterol molecule to stabilize the siRNA so it could penetrate the cell membrane and be injected into the mice.
“We used the cholesterol molecule as kind of a Trojan horse to bring the siRNA into cells,” Vornlocher said.
John Rossi, of the Beckman Research Institute of the City of Hope in Duarte, California said the use of cholesterol helped the cells to take up the siRNA.
“The beauty of these results is the relative simplicity of the delivery method,” he said in a commentary in the journal.
Unlike most drugs which block the action of proteins, RNAi interferes with their production. Maraganore compared the two approaches to dealing with a flood.
“Our approach is to turn off the faucet whereas today’s medicines are mopping up the floor,” he said.
“The technology we established to generate these breakthrough results enables for the first time the potential for RNAi therapeutics to be developed to address significant diseases such as cardiovascular disease, diabetes, obesity, hepatitis, cancer and many infectious diseases,” Maraganore added.