Knockdown of different influenza A virus subtypes in cell culture by a single antisense oligodeoxyribonucleotide

• A single oligonucleotide efficiently inhibited various influenza A virus (IAV) strains.
• Oligonucleotide is delivered into cells in a TiO2·PL–DNA nanocomposite.
• Oligonucleotide is targeted to the IAV genome region common to all tested IAV strains.

Influenza is a heavy socially significant viral infection that affects humans, birds, and wild and domestic animals. The threat of existing and new highly pathogenic subtypes of influenza A virus (IAV) makes it necessary to develop an effective drug that may affect different IAV strains. For this purpose, oligodeoxynucleotides (DNA fragments) attached to titanium dioxide (TiO2) nanoparticles through a polylysine linker, forming TiO2·PL–DNA nanocomposites, that penetrated into cells without transfection agents were used. For the first time, efficient (≥99.9%) suppression of the reproduction of different subtypes of IAV, including highly pathogenic H5N1 and H1N1, was achieved. These results were obtained using the TiO2·PL–DNA nanocomposite bearing a single antisense oligodeoxynucleotide (0.1 μM) targeted to the conserved 3′-noncoding region of RNA segment 5, which is common to all tested strains. Very efficient suppression of the reproduction of different subtypes of IAV was probably achieved due to the use of the proposed delivery system for oligonucleotides in the form of the TiO2·PL–DNA nanocomposites. These results indicate the possibility of creating an efficient drug to affect existing and newly emerging pathogenic IAV strains.