Scientists have taken an important step towards a new way of treating disease by switching off key genes.
The technique interferes with gene function
The research, tested in mice by biotechnology company Alnylam Pharmaceuticals, blocks cells' ability to manufacture proteins.
It resulted in cholesterol levels being almost halved, and it is hoped the same approach could eventually treat many diseases from diabetes to cancer.
Details are published in the journal Nature.
The genes in our DNA are the cell's instructions for how to make proteins, the sophisticated molecules that build and maintain our bodies.
The researchers were able to interfere with an intermediate stage of this process and, in doing so, effectively silence a gene associated with cholesterol.
So-called "RNA interference therapy" is difficult so this first animal success is considered a significant achievement and a proof in principle that it may also work in people.
If so - and assuming there are no side effects - then the technique has enormous potential for medical treatments by switching off the genes that cause a wide range of diseases.
Writing in the same edition of Nature, Dr John Rossi, a molecular biologist at the Beckman Research Institute, said it was remarkable that only a few years after the discovery of RNA interference, scientists had come up with a potential way to manipulate it to treat disease.
"It remains to be seen whether the cholesterol-conjugate approach can be used to silence other disease-related genes in animal models," he said.
"If so, it should revolutionise the use of RNA interference."
Dr Julian Downward, from the charity Cancer Research UK, said: "This is a very exciting development in the design of new therapies for human diseases.
"For the first time, it harnesses the great potency that RNA interference has shown in the lab to a format that can be used in patients in the clinic.
"This brings the prospect of uniquely targeted therapies a big step closer, even for diseases that have previously proven hard to develop conventional drugs against."
RNA interference is a phenomenon in which the production of proteins within a cell is disrupted by short strands of genetic material called "short interfering" RNA (siRNA).
The medical potential from manipulating this process artificially is huge but delivering siRNAs into cells is extremely difficult.
They tend to be damaged or destroyed before reaching their target.
Some success has been achieved by injecting them directly into a specific organ, such as the eye.
But RNA interference will only ever really be practical if it can be administered like conventional medicines.
The German scientists were able to give siRNAs drug-like properties by joining them to molecules of cholesterol.
Together with some other changes, this allowed the siRNAs to bind to proteins
in the blood, increasing their stability 15-fold.
The fatty cholesterol molecule also helped them to sneak inside cells.
The scientists used the approach to try to disrupt production of cholesterol by targeting apolipoprotein B (apoB), a key protein in its manufacture.
Mice were injected with a cholesterol-linked siRNA specifically designed to block production of the protein.
Blood levels of apoB protein dropped by nearly 70% and cholesterol levels plunged.
The treated mice had cholesterol readings similar to other animals whose apoB gene had been completely deleted.