FL (Jan. 19, 2005)-- 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.
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.
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."
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.
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.
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.
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.
Anne DeLotto Baier
University of South Florida Health Sciences Center