Treating STDs with a nanotech knockout

YALE (US)—Using specialized RNA molecules to interfere and silence—or knock out—genes could be the first step in developing a new type of treatment for sexually transmitted diseases (STDs).

Yale University researchers designed small interfering RNA molecules, or siRNAs, to target a gene expressed widely in the lining of the female mouse reproductive tract. Using densely-loaded nanoparticles made of a biodegradable polymer known as PLGA, the researchers created a stable “time release” vehicle for delivery of the tiny molecules to sensitive mucosal tissue—like that of the female reproductive system.

“RNA interference is a promising approach for prevention and treatment of human disease,” says lead author Kim Woodrow, a postdoctoral fellow in Yale’s School of Engineering & Applied Science. “We wanted to develop a new strategy of delivering siRNAs with a FDA-approved material.”

The Yale team found that the nanoparticles, loaded with the drug agent, moved effectively in two important ways, penetrating to reach cells below the surface of the mucosa and distributing throughout the vaginal, cervical, and uterine regions. Additionally, the siRNAs stayed in the tissues for at least a week and knockdown of gene activity lasted up to 14 days.

Gene interference therapy is moving rapidly from basic research to application. The PLGA packaging the researchers chose is already approved as safe and nontoxic by the FDA, speeding the path to clinical trials for infectious agents such as HPV and HIV.

“Before human clinical testing can begin, our next step in research will be to test this approach directly in disease models—for example, in the HIV model mice that have an immune system genetically identical to humans,” says senior author W. Mark Saltzman, the Goizueta Foundation Professor of Biomedical Engineering & Chemical Engineering.

This approach holds promise for global health and the ability of people to self–apply antimicrobial treatments. Woodrow adds, “It is safe and effective and much easier than getting an injection of vaccine.”

The research was funded by grants from the National Institutes of Health and fellowship support from the L’Oreal FWIS. The work was reported May 4 in the online publication of Nature Material.

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