The safety and effectiveness of RNA interference has been proven in the clinic
RNA interference was used to fight a deadly disease
The conducted clinical trials have shown not only the ability to quickly reduce the level of the life-threatening protein of the patient, but also allowed us to draw preliminary conclusions about the safety of the drug based on the phenomenon of RNA interference. Details are given in an article for The New England Journal of Medicine (Coelho et al., Safety and Efficacy of RNAi Therapy for Transthyretin Amyloidosis).
During therapy, scientists synthesized short single-stranded RNA fragments, placed them in liposomes and injected them into the blood of patients. The sequence of interfering RNAs (siRNAs) was complementary to one of the sites of the transtiretin protein matrix RNA, the increased synthesis of which in the liver leads to one of the forms of amyloidosis. The molecules joined together formed double-stranded fragments, which were then actively destroyed by the cell. As a result, the synthesis of transthyretin slowed down or stopped completely, and this effect persisted for several weeks.
The most well-known variant of amyloidosis (strictly speaking, these are several different diseases) is Alzheimer's disease. This study involved patients with transthyretin amyloidosis, who primarily suffer from the liver, where excess protein is synthesized. However, even a liver transplant is unable to completely cure patients, as transthyretin continues to be synthesized in other organs.
During therapy, the decrease in the level of transthyretin reached 80 percent in some patients (with one of several mutations, see the graph from the article in NEJM – VM) and sometimes remained at twice the initial level for 28 days.
Healthy volunteers who were injected with an experimental drug, at the same time faced only minor allergic reactions at the time of intravenous administration of the drug. According to independent experts, whose opinion is cited by Science Now (RNAi Treatment Steps Up), the new data allow us to transfer the RNA interference method from the research category to the medical category. At the same time, experts emphasize that it may not always be as effective: "Fat capsules are well absorbed by liver cells, but it is unclear to me how they will act on other tissues," says molecular genetics specialist John Rossi.
In laboratory conditions, RNA interference is used to selectively disable the synthesis of proteins of interest to researchers. In nature, the same process is responsible for the fight of cells against certain viruses and for the regulation of gene expression.
Portal "Eternal youth" http://vechnayamolodost.ru02.09.2013