Challenging a long-held convention, University researchers have shown they can inhibit the influenza A virus by targeting its genomic RNA with “antisense” compounds.
Their findings, highlighted on the cover of Nucleic Acid Therapeutics, offer scientists a new way to attack an increasingly drug-resistant pathogen that causes an estimated 250,000 to 500,000 deaths a year.
“Antisense” compounds are synthesized with nucleotides, the building blocks of nucleic acid, often shown as various combinations of A, U, G and C. When the compounds – called antisense oligonucleotides (ASOs) – bind to the targeted genomic RNA, they block its ability to replicate.
The collaboration, involving the labs of Douglas Turner, professor of chemistry; Luis Martinez-Sobrido, associate professor of microbiology and immunology; and two researchers in Poland, reported that “antisense” compounds targeting one of the virus’ eight genomic RNA segments caused a five- to 25-fold reduction of influenza A virus in cell cultures.
“That’s a big difference,” Martinez-Sobrido says. “When mice are infected with 10,000 viruses, they all die. However, with 25 times less virus, all animals can survive infection and they don’t even develop symptoms.”