Hope for treating dengue virus is provided by new mRNA and gene editing technologies.

The dengue virus, which is commonly known in tropical nations as a painful and occasionally lethal mosquito-borne illness, is spreading quickly throughout the world. There is now no effective antiviral treatment for the disease, and 4 billion people dwell in areas like the Southeast of the United States that are at risk for contracting it.

A group of scientists under the direction of biomedical engineer Phil Santangelo have created a ground-breaking treatment that uses the CRISPR-Cas13 gene editing technique to specifically target and eliminate the virus. The researchers report that in a study published in Nature Microbiology, they were able to successfully treat dengue virus in mice by administering the medication systemically.

The fact that there are four distinct virus serotypes, which translates to four distinct vaccination targets, contributes to the difficulty of treating dengue. When a person with one serotype infection gets infected with a second virus, they run the risk of developing a serious illness. It's possible that the second attack will exacerbate the first. Fever, nausea, rash, aches and pains (especially behind the eyes), and in rare instances, internal hemorrhage, shock, and even death are among the symptoms.

"Treating dengue presents a number of difficulties, so we wondered if we could develop an mRNA-based, CRISPR-based antiviral where the virus could be eradicated with a single shot," explained Santangelo, a professor at Georgia Tech's Wallace H. Coulter Department of Biomedical Engineering and Emory University. "And that's basically what we've shown."

"Treating dengue presents a number of difficulties, so we wondered if we could develop an mRNA-based, CRISPR-based antiviral where the virus could be eradicated with a single shot," explained Santangelo, a professor at Georgia Tech's Wallace H. Coulter Department of Biomedical Engineering and Emory University. "And that's basically what we've shown."

For the first time, systemic viral infections in animal models have been successfully treated with an mRNA-based CRISPR therapy. However, Santangelo proved its effectiveness in prior research on lung conditions, such as a coronavirus treatment. Polymeric nanoparticles, which are big, biodegradable molecules perfect for delivering medication directly to the lungs, were used in that inhalable treatment.

Lipid nanoparticles (LNPs), which are similar to microscopic fat bubbles that carry medications into cells and through the circulation, were employed by the scientists for the dengue virus study. A messenger RNA (mRNA) molecule with a unique coding was transported by the nanoparticles.

The CRISPR protein Cas13a, which can cut viral RNA, and guide RNAs, which point Cas13a in the direction of the viral RNA to be cut, were encoded into the mRNA. In essence, the procedure produced a collection of instructions. Upon delivery of the encoded mRNA to the infected cells through LNPs, the cell utilized the instructions to assemble Cas13a and guide RNAs, thereby causing the viral RNA within the targeted cells to be broken down.