New RNA therapy is administered through the nasal cavity and is expected to treat viral infections

April 12, 2018 Source: WuXi PharmaTech

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A team of researchers at Yale University and Hanyang University in Korea has developed a novel RNA therapy for West Nile Virus (WNV). Recently, an article published in "Cell Host & Microbe" proposed a breakthrough treatment strategy after WNV invaded the brain and central nervous system.

WNV disease is a mosquito-borne disease and there are currently no approved vaccines or effective treatments. According to the Centers for Disease Control and Prevention (CDC), about one-fifth of WNV-infected people have fever and other symptoms. Most people with fever can have fever, headache, body aches, joint pain, vomiting, diarrhea or rash. Although most patients can fully recover, fatigue and weakness often last for weeks to months. About one in every 150 infected people, especially young people and the elderly, may have serious neurological problems and even death. The sporadic nature of this disease makes it extremely difficult to develop and evaluate vaccines.

To investigate new ways to treat WNV infection, Yale researchers have developed a small "interfering" RNA molecule that limits viral infection by targeting conserved sequences within the WNV E protein. In order to direct RNA to infected cells, they are packaged in rabies virus-derived peptides to allow them to enter nerve cells. This therapy is administered through the nose to avoid the brain barrier.

â–² Treatment of WNV virus infection by siRNA (Source: "Cell Host&Microbe")

The researchers demonstrated that the use of a rabies-derived neuronal targeting peptide (RVG9R) and intranasal administration of the small interfering RNA siFvEJW to the central nervous system restored late-infected mice infected with WNV. The use of viruses that selectively target the central nervous system reduces the amount of virus in the brain and reduces neuropathy. The mice survived for 5-6 days (viral titers peaked in the central nervous system) with a survival rate of 90%, whereas placebo-treated mice died at 9-10 days. Importantly, clearance of central nervous system virus is achieved in peripheral tissues by humoral and cell-mediated immune responses, which also immunizes subsequent WNV infections. These results indicate that intranasal RVG9R-siRNA therapy provides effective treatment and promotes natural long-term immunity to neuroinvasive viruses.

"This treatment prevents lesions in the brain and gives mice a strong immune response." Dr. Priti Kumar, a principal investigator at the Yale University School of Medicine, said: "In translation medicine, it should be an effective Strategy. Although the anatomy of the mouse's nose is different from that of humans, the researchers plan to further study the therapy and hope to be widely used. The researchers pointed out that in theory, intranasal RNA therapy can be developed to treat other mosquito-borne diseases such as St. Louis encephalitis, Japanese encephalitis and Zika virus.

We expect this therapy to be used early in the clinic to find a solution to the neuroinvasive disease of viral infection.

Note: The title map source 123RF

Reference materials:

[1] Small Interfering RNA-Mediated Control of Virus Replication in the CNS Is Therapeutic and Enables Natural Immunity to West Nile Virus

[2] Researchers Develop Possible New RNA Therapy for West Nile Virus

[3] Novel RNA-based therapy to target West Nile virus developed

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