title: Knockdown of different influenza A virus subtypes in cell culture by a single antisense oligodeoxyribonucleotide.
abstract: 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 (0.1μM) 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.
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, pr. Lavrent'eva 8, Novosibirsk 630090, Russia.
authors.forename: Asya S
authors.initials: AS
authors.lastname: Levina
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, pr. Lavrent'eva 8, Novosibirsk 630090, Russia.
authors.forename: Marina N
authors.initials: MN
authors.lastname: Repkova
authors.affiliation: FBRI State Research Center of Virology and Biotechnology, 'Vector', Koltsovo, Novosibirsk 630559, Russia.
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Mazurkova
authors.affiliation: FBRI State Research Center of Virology and Biotechnology, 'Vector', Koltsovo, Novosibirsk 630559, Russia.
authors.forename: Elena V
authors.initials: EV
authors.lastname: Makarevich
authors.affiliation: Institute of Catalysis, Siberian Branch of Russian Academy of Sciences, pr. Lavrent'eva 5, Novosibirsk 630090, Russia.
authors.forename: Zinfer R
authors.initials: ZR
authors.lastname: Ismagilov
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, pr. Lavrent'eva 8, Novosibirsk 630090, Russia. Electronic address: Levina@niboch.nsc.ru.
authors.forename: Valentina F
authors.initials: VF
authors.lastname: Zarytova
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism*; D018929:Cell Culture Techniques; D004285:Dogs; D004337:Drug Carriers / Q000378:metabolism; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000502:physiology; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects* / Q000502:physiology; D061985:Madin Darby Canine Kidney Cells; D053758:Nanoparticles / Q000378:metabolism; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics* / Q000378:metabolism*; D014025:Titanium / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D004337:Drug Carriers; D020319:Oligodeoxyribonucleotides, Antisense; C009495:titanium dioxide; D014025:Titanium
keywords: DNA fragments; Influenza A virus; Nanocomposite; TiO(2) nanoparticles