Novel antiviral technology inhibits RSV infection in mice

A novel antiviral treatment combining nanoparticle and gene silencing technologies thwarts attacks of respiratory syncytial virus (RSV) — a virus associated with severe bronchitis and asthma, an animal study by University of South Florida researchers found. The study was reported in the January 2005 issue of the journal Nature Medicine.

RSV infects lung cells and can be life-threatening in very young children, the elderly and those with compromised immune systems. No vaccine or widespread antiviral treatment is available for the infection.

Researchers at USF’s Joy McCann Culverhouse Airway Disease Research Center, working with scientists from the Moffitt Cancer Center and TransGenex Nanobiotech Inc., used a revolutionary new technology known as RNA interference, or gene silencing, to knock out one of the key proteins needed for RSV to multiply in the lungs. The virus harnesses this protein, known as NS1, to block the body’s own antiviral response, which would normally kill RSV before it could gain a foothold.

“This is an exciting advance in the fight against respiratory syncytial virus infection,” said Shyam S. Mohapatra, PhD, principal investigator of the study and director of basic research at the USF Division of Allergy and Immunology. “We found that RNA interference targeting a virus’s NS1 gene can be administered in the form of a nasal drop or spray. The treatment keeps the host’s natural antiviral shield intact and attenuates virus reproduction, providing substantial protection from severe infections over days to weeks.”

Dr. Mohapatra and his team developed nose drops containing vectors capable of producing small fragments of RNA (siRNA). These fragments were encapsulated within chitosan nanoparticles — miniscule naturally-occurring, biodegradable particles that stick to mucous-producing cells lining the lungs. The RNA produced is specifically designed to suppress the protein NS1. Without NS1, the host antiviral defense remains intact and the virus cannot reproduce.

Mice treated intranasally with the gene-silencing nanoparticles, before and after infection with RSV, showed significantly lower levels of virus in the lung and less airway inflammation and hyper-reactivity than untreated mice.

The study was supported by grants from the Veterans’ Affairs Merit Review Award and the Joy McCann Culverhouse Endowment. Other study authors were Weidong Zhang, Hong Yhang, Xiaoyuan Kong, Subhra Mohapatra, Homero San Juan-Vergara, Gary Hellermann, Sumita Behera, Rejeswari Singam and Richard F. Lockey.

Dr. Mohapatra is also a molecular biologist at the James A. Haley Veterans’ Hospital and a member of the scientific advisory board of TransGenex Therapeutics Inc., a USF spin-out company developing polymeric nanoparticles as a drug delivery platform.