In the experiments, eight Neugene antisense compounds were developed to target regions of the influenza virus genome believed to be critical to virus survival. AVI also selected regions of the virus that are highly conserved across all six virus subtypes that cause human disease.
Several agents that were both potent and specific for influenza A have been identified as suppressing replication of H1N1 (Spanish flu). One agent was found to inhibit both viral transcription and replication.
Moreover, combinations of two agents were routinely twofold to threefold more active than single agents alone, and one combination of two agents exhibited sevenfold to eightfold improvement in viral reduction compared with a single agent.
Additional experiments showed that a single mismatch within the targeted region of the virus caused less than a 10 percent loss of activity of the drug. This provides strong evidence that a single Neugene antisense drug could potentially shut down all the flu virus subtypes, including the H5N1 avian flu, even if a mutation occurred in these highly conserved regions.
AVI targeted regions of the virus genome that are highly conserved between six viral subtypes that cause human disease. These include three subtypes that caused pandemics in the 20th century – the 1918 Spanish flu (H1N1), the 1957 Asian flu (H2N2) and the 1968 Hong Kong flu (H3N2) – and three subtypes of avian flu that have been reported to cause disease in man (H5N1, H7N7 and H9N2).
“Several of these Neugene compounds have been efficacious in early experiments and should now be considered for in vivo evaluation against H1N1 and H5N1,” said Dr Denis Burger, CEO of AVI. “AVI has a successful track record of developing antisense drug candidates against RNA viruses quickly – what we refer to as our rapid response therapeutic platform.”