Mark Saltzman, chair of the biomedical engineering department of the Yale School of Medicine, and researchers in his laboratory have been working to develop nanoparticles to decrease symptom severity and boost survival rates of mice with HSV-2. Saltzman and his colleagues published a paper in the August issue of the “Journal of Controlled Release” in which they state that administering three doses of siRNA nanoparticles improved survival rates for mice infected with HSV-2.
By delivering siRNA molecules to the site of infection, these nanoparticles reduce the expression of the nectin-1 protein involved in HSV-2 infection and cell-to-cell transmission. As a result, HSV-2 is less likely to enter cells surrounding the site of infection.
“This work provides proof-of-concept that these siRNA delivery vehicles are promising options for topical, localized therapeutics for sexually transmitted infections,” postdoctoral researcher Jill Steinbach said in an October press release. Steinbach, the lead author of the paper, told the News on Sunday that administration of nanoparticles increased the amount of time mice could live with the disease to an “unprecedented 28 days.”
Administration of nanoparticles can cause inflammation and leave patients susceptible to additional infections, an issue that has hindered similar experiments in other labs, Steinbach said. The researchers successfully decreased inflammation in mice by using an FDA-approved, biodegradable non-toxic polymer — polylactic co-glycolic acid, she added.
Saltzman’s lab specializes in drug delivery, particularly in transmitting nanoparticles across the blood-brain barrier and across mucosal surfaces such as the intervaginal wall. Biomedical engineering Ph.D. candidate Rachel Fields GRD ’13, who works in Saltzman’s lab, said this lab is one of many working to identify diseases that can be treated using nanoparticles. Saltzman’s research team currently includes seven graduate students as well as four postdoctoral researchers.
“The lab is like a family and we all collaborate and support one another’s research,” molecular physiology Ph.D. candidate Kseniya Gavrilov GRD ’15 said. “Professor Saltzman is a wonderful mentor, and he doesn’t micromanage, but expects all of us to be responsible and not waste time or resources.”
Saltzman and his colleagues seek to improve upon their work by developing surface modifications that will advance nanoparticle delivery, easing cell penetration. Steinbach said the researchers are currently working on attaching peptides to the nanoparticle surfaces to increase cell binding and internalization, boosting the efficacy of the nanoparticles. Researchers also said they hope their use of FDA-approved, non-toxic materials in the nanoparticles will permit quicker licensing of the treatment for humans suffering from HSV-2.
“We are hopeful to further improve delivery of these materials and apply them to a wide range of pathologies in global health,” Steinbach said in the press release.
HSV-2 infects one of every six people between the ages of 14 and 49 in the United States, according to the Center for Disease Control.