Substantial Antiviral Potential of Deoxyribozymes Fixed on Anatase Nanoparticles Against Influenza A Viruses in vitro and in vivo.

Influenza A viruses (IAV) are a high threat to humanity because of a lack of proper effective antiviral drugs and resistance of viruses to existing vaccines. We describe the sufficient anti-IAV effect of Ans/PL-Dz nanocomposites that contain deoxyribozymes (Dz) immobilized on anatase TiO nanoparticles (Ans) through polylysine linker (PL). The Dz-containing nanocomposites appear to be more efficient than the Ans/PL-ODN nanocomposites that contain common oligodeoxyribonucleotides (ODN) targeted to the same RNA regions of the viral genome.

Effective Inhibition of Newly Emerged A/H7N9 Virus with Oligonucleotides Targeted to Conserved Regions of the Virus Genome.

Newly emerged highly pathogenic A/H7N9 viruses with pandemic potential are effectively transmitted from birds to humans and require the development of novel antiviral drugs. For the first time, we studied the and antiviral activity against A/H7N9 of oligodeoxyribonucleotides (ODNs), which were delivered into the cells in the proposed TiO-based nanocomposites (TiO∼ODN). The highest inhibition of A/H7N9 (∼400-fold) and efficient, sequence-specific, and dose-dependent protection (up to 100%) of A/H7N9-infected mice was revealed when ODN was targeted to the conserved terminal 3'-noncoding region of viral (-)RNA.

Pronounced therapeutic potential of oligonucleotides fixed on inorganic nanoparticles against highly pathogenic H5N1 influenza A virus in vivo.

This study describes the effective attack of oligonucleotides on the viral genome of highly pathogenic H5N1 influenza A virus (IAV) in vivo using for the first time the new delivery system consisting of biocompatible low-toxic titanium dioxide nanoparticles and immobilized polylysine-containing oligonucleotides with the native (ODN) and partially modified (ODN) internucleotide bonds. Intraperitoneal injection of the TiO•PL-ODN nanocomposite provided 65-70% survival of mice, while intraperitoneal or oral administration of TiO•PL-ODN was somewhat more efficient (~80% survival). The virus titer in the lung was reduced by two-three orders of magnitude.

Non-agglomerated silicon-organic nanoparticles and their nanocomplexes with oligonucleotides: synthesis and properties.

The development of efficient and convenient systems for the delivery of nucleic-acid-based drugs into cells is an urgent task. А promising approach is the use of various nanoparticles. Silica nanoparticles can be used as vehicles to deliver nucleic acid fragments into cells.

Efficient inhibition of influenza A viral replication in cells by deoxyribozymes delivered by nanocomposites.

Nucleic-acid-based drugs are a promising class of novel therapeutics; however, their use in medicine is widely limited because of insufficient delivery into cells. This article proposes a new delivery strategy of nucleic acid fragments into cells as components of TiO-based nanocomposites. For the first time, unmodified Dz molecules were non-covalently immobilized on TiO nanoparticles precovered with polylysine (TiO•PL) with the formation of (TiO•PL)•Dz nanocomposites.

High antiviral effect of TiO·PL-DNA nanocomposites targeted to conservative regions of (-)RNA and (+)RNA of influenza A virus in cell culture.

The development of new antiviral drugs based on nucleic acids is under scrutiny. An important problem in this aspect is to find the most vulnerable conservative regions in the viral genome as targets for the action of these agents. Another challenge is the development of an efficient system for their delivery into cells.

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

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.

SiO₂ nanoparticles as platform for delivery of 3'-triazole analogues of AZT-triphosphate into cells.

A system for delivery of analogues of AZT-triphosphates (AZT*TP) based on SiO₂ nanoparticles was proposed. For this purpose, a simple and versatile method was developed for the preparation of SiO₂∼dNTP conjugates using the 'click'-reaction between AZTTP and premodified nanoparticles containing the alkyne groups. The substrate properties of SiO₂∼AZT*TP were tested using Klenow fragment and HIV reverse transcriptase.

SiO₂ nanoparticles as platform for delivery of nucleoside triphosphate analogues into cells.

A system for delivery of analogues of 2'-deoxyribonucleoside triphosphate (dNTP) based on SiO(2) nanoparticles was proposed. A simple and versatile method was developed for the preparation of SiO(2)-dNTP conjugates using the 'click'-reaction between premodified nanoparticles containing the azido groups and dNTP containing the alkyne-modified γ-phosphate group. The substrate properties of SiO(2)-dNTP were tested using Klenow fragment and HIV reverse transcriptase.

High-performance method for specific effect on nucleic acids in cells using TiO2~DNA nanocomposites.

Nanoparticles are used to solve the current drug delivery problem. We present a high-performance method for efficient and selective action on nucleic acid target in cells using unique TiO(2)·PL-DNA nanocomposites (polylysine-containing DNA fragments noncovalently immobilized onto TiO(2) nanoparticles capable of transferring DNA). These nanocomposites were used for inhibition of human influenza A (H3N2) virus replication in infected MDCK cells.

Nanocomposites consisting of titanium dioxide nanoparticles and oligonucleotides.

The use of various nanoparticles is a promising way to solve the current problem of drug delivery in medicine and biology. Nanocomposites consisting of titanium dioxide and oligonucleotides noncovalently attached to nanoparticles through the polylysine linker (TiO2 x PL-DNA) have been designed to deliver of DNA fragments into cells. Three forms of TiO2 nanoparticles (amorphous, anatase, and brookite) were used for construction of nanocomposites.

Oligonucleotide probes containing polylysine residues for fabrication of DNA chips on various solid surfaces.

Various materials, such as glass, plastic, metals, etc., are utilized for preparing DNA chips. In each particular case special approaches are used for immobilization of different oligonucleotide derivatives on the solid supports.

Preparation of DNA chips using polyamine-oligonucleotide conjugates.

A convenient and efficient method for three-dimensional immobilizing oligonucleotides on glass was developed using oligonucleotide derivatives bearing a polyamine linker (PA-oligo conjugates). Polyamine (polylysine, poly(lysine, phenylalanine), polyethyleneimine) residues stipulate durable fixation of such conjugates to the glass surface with a high yield (90-95%). A DNA fragment (414-mer) is hybridized specifically to an immobilized oligonucleotide.

Site-specific cleavage of RNA and DNA by complementary DNA--bleomycin A5 conjugates.

Bleomycin displays clinical chemotherapeutic activity, but is so nonspecifically toxic that it is rarely administered. It was therefore of interest to determine whether bleomycin could be directed to cleave RNA or DNA at a specific site by conjugation to a complementary oligonucleotide. A 15 nt MYC complementary oligodeoxynucleotide (HMYC55) bearing a 5' bleomycin A5 (Blm) residue was designed to base-pair with nt 7047-7061 of human MYC mRNA.