New delivery technology paves way for disease therapies

A new way to administer therapeutic RNA molecules that efficiently guides them to cells throughout the body is being reported by researchers at the Harvard-affiliated CBR Institute for Biomedical Research and Harvard Medical School (HMS). The technique couples the homing ability of antibodies and an avid RNA-binding protein from sperm to deploy the RNAs in the bloodstream, where they can find and slip into their target cells.
The technique will speed the clinical application of RNA interference (RNAi), a recently discovered process of selective gene silencing that is expected to yield exquisitely focused therapies for many human diseases, including cancer and AIDS. Development of RNA therapeutics has been hung up on the practical matter of how to deliver these drugs to inaccessible organs and tissues, and in what way that cells will be able to absorb them.

"This method allows us to inject an RNA drug intravenously and get it throughout the body, and then to deliver it to certain cells very specifically and with very high efficiency," said Judy Lieberman, senior investigator at the CBR Institute for Biomedical Research and professor of pediatrics at HMS, and principal author of the study.

Lieberman and her colleagues used their new system to show for the first time that infusing small interfering RNAs (siRNAs) coupled to cancer-seeking antibodies slows the growth of tumors in mice while leaving the surrounding normal tissue untouched. The researchers also demonstrate that siRNAs targeted to immune system T cells infected with HIV, but not healthy T cells, block viral growth. Their work will appear May 22 online in Nature Biotechnology.

"We are developing reagents that are useful for targeting immune cells, erythroid cells, liver cells, and brain cells. The ability to target antibodies is pretty unlimited, and that's why it's so attractive, since we can think of whole classes of disease where the RNA interference approach might be useful," Lieberman said.