A dramatic new study published in the most recent issue of Nature questions some of the mechanisms underlying a new class of drugs based on Nobel Prize-winning work designed to fight diseases ranging from macular degeneration to diabetes.
Dr. Jayakrishna Ambati, a University of Kentucky researcher and the paper's senior author, has for years been investigating gene silencing, a 1998 discovery that won a Nobel Prize in Physiology or Medicine in unusually quick fashion in 2006.
While the prize-winning discovery remains important, the findings made by Ambati's lab show the mechanisms behind it are not as scientists once believed. In fact, Ambati's work imparts the need for caution in current clinical trials using the technology, as it may have potentially harmful effects on subjects.
Gene Silencing Leads to New Class of Drugs
In short, researchers in 1998 discovered a class of double-stranded RNA (dsRNA) that possessed powerful gene-silencing capabilities, or the ability to "turn off" disease-causing genes in the body.
The technique of targeting these dsRNA for single genes was refined with synthetic molecules called small-interfering RNA (siRNA). siRNA were thought to have the capability to interfere with specific disease-causing genes and prevent them from being expressed.
Because gene-targeted silencing with siRNA does not involve permanent DNA mutations, this approach rapidly gained popularity throughout biomedical research. The breakthrough, with the powerful ability to turn off genes, has become a standard research tool for genetic studies and has resulted in a new class of 21st century drugs designed to silence disease-causing genes in the body or disarm an invading virus by knocking out its genes.
Many diseases including age-related macular degeneration, diabetes, kidney disease, cancer, Lou Gehrig's and Parkinson's have been heralded as candidates for siRNA therapy, creating a wave of on-going clinical trials.