Oral delivery system of small interfering RNAs
In the April 30, 2009 issue of Nature, information was published about a new development by the staff of the Medical School at the University of Massachusetts. Professor Michael P. Czech (Michael P. Czech) and colleagues described microscopic capsules developed within the framework of the molecular medicine program containing small interfering RNAs (miRNAs) capable of silencing a certain gene at the level of its translation into a protein product. The development described in the article makes it possible to achieve RNA interference with oral administration of the miRNA drug, which has been demonstrated in mice. The data obtained suggest a new way to solve the most pressing issue in the field of RNA therapy - the issue of targeted delivery of miRNA to certain tissues and cell types.
The discovery of small interfering RNAs in 1998 turned the scientific world's ideas about the regulation of gene activity upside down. Highly specific and extremely effective RNA interference technique quickly took its place among laboratory techniques. Since miRNAs are highly specific, non-toxic and cause minimal immune response, the potential of RNA interference as a therapeutic tool is of particular interest. The explanation of the mechanism of action of miRNA, formulated by Professor Craig C. Mello from the University of Massachusetts and Dr. Andrew Z. Fire from Stanford University, was awarded the 2006 Nobel Prize in Medicine.
But until now, targeted delivery of miRNA within a living organism has remained an unsolvable problem. The developers of the new system have targeted macrophages – white blood cells that play an important role in the immune response, including in such widespread diseases as rheumatic arthritis and atherosclerosis.
In their work, the researchers relied on the ability of macrophages to recognize yeast cells and absorb them. A method has been developed for cleaning the membranes of yeast cells and synthesizing microcapsules from beta-1,3-D-glucan, a polysaccharide entering the cell wall of yeast and other fungi, which is almost not destroyed in the food tract and is well recognized by the immune system as a foreign substance, but does not cause an acute immune response (beta–glucan is even included in the composition many dietary supplements as an anti-inflammatory component). These microscopic containers were filled with miRNA molecules suppressing the expression of one of the genes that play a key role in the development of the inflammatory process. When ingested into the digestive tract, the particles are partially absorbed by macrophages, which then circulate throughout the body along with the bloodstream. Thus, after some time, most of the macrophages contain miRNA, and the target gene is not synthesized in them.
During the experiments, the researchers achieved the effect of RNA interference both in vitro and in vivo on a number of animal models, using different doses and concentrations. With the method of oral administration, 20 micrograms of miRNA per kilogram of body weight turned out to be enough to stop the work of the target gene. For comparison, with intravenous administration of miRNAs, 12-500 times higher concentrations are often used.
The described development is considered as a landmark in the field of RNA therapy and has earned attention and financial support from a number of sources. The research will be continued in the near future.
Portal "Eternal youth" www.vechnayamolodost.ru Based on ScienceDaily: Oral Delivery System For RNAi Therapeutics07.05.2009