A5028266747- RNA Interference and Gene Delivery
- Advanced biosensing and bioanalysis techniques
- MicroRNA in disease regulation
- DNA and Nucleic Acid Chemistry
- Extracellular vesicles in disease
- Dendrimers and Hyperbranched Polymers
- Virus-based gene therapy research
- Immunotherapy and Immune Responses
- Cancer therapeutics and mechanisms
- Morinda citrifolia extract uses
- Monoclonal and Polyclonal Antibodies Research
- Adipose Tissue and Metabolism
- Bioactive Compounds and Antitumor Agents
- CAR-T cell therapy research
- Nanoparticle-Based Drug Delivery
- Biopolymer Synthesis and Applications
- Helicobacter pylori-related gastroenterology studies
- Neonatal Respiratory Health Research
- Pharmacological Effects of Natural Compounds
- Phytochemistry and biological activity of medicinal plants
- Polyamine Metabolism and Applications
- Biosimilars and Bioanalytical Methods
- Inflammasome and immune disorders
- Neurobiology and Insect Physiology Research
- Cytokine Signaling Pathways and Interactions
Siberian Branch of the Russian Academy of Sciences
2017-2024
Institute of Chemical Biology and Fundamental Medicine
2017-2024
The conjugation of siRNA to molecules, which can be internalized into the cell via natural transport mechanisms, result in enhancement cellular uptake. Herein, carrier-free uptake nuclease-resistant anti-MDR1 equipped with lipophilic residues (cholesterol, lithocholic acid, oleyl alcohol and litocholic acid oleylamide) attached 5′-end sense strand oligomethylene linker various length was investigated. A convenient combination H-phosphonate phosphoramidite methods developed for synthesis...
Chemical modifications are an effective way to improve the therapeutic properties of small interfering RNAs (siRNAs), making them more resistant degradation in serum and ensuring their delivery target cells tissues. Here, we studied carrier-free biodistribution biological activity a nuclease-resistant anti-MDR1 cholesterol-siRNA conjugate healthy tumor-bearing severe combined immune deficiency (SCID) mice. The attachment cholesterol siRNA provided its efficient accumulation liver tumors,...
Acute lung injury is a complex cascade process that develops in response to various damaging factors, which can lead acute respiratory distress syndrome. Within this study, based on bioinformatics reanalysis of available full-transcriptome data induced mice and humans by we selected set genes could serve as good targets for suppressing inflammation the tissue, evaluated their expression cells different origins during LPS-induced inflammation, chose tissue inhibitor metalloproteinase Timp1...
After decades of nonspecific lymphoma therapy, personalized approaches such as described here are on the horizon.
Cholesterol siRNA conjugates attract attention because they allow the delivery of into cells without use transfection agents. In this study, we compared efficacy and duration silencing induced by cholesterol selectively totally modified siRNAs their heteroduplexes same sequence explored impact linker length between 3′ end sense strand on activity “light” “heavy” siRNAs. All 3′-cholesterol were equally active under transfection, but conjugate with a C3 was less than those longer linkers (C8...
Small interfering RNA (siRNA) holds significant therapeutic potential by silencing target genes through interference. Current clinical applications of siRNA have been primarily limited to liver diseases, while achievements in delivery methods are expanding their various organs, including the lungs. Cholesterol-conjugated emerges as a promising approach due its low toxicity and high efficiency. This study focuses on developing cholesterol-conjugated anti-
Biological activity of antisense oligonucleotides (asON), especially those with a neutral backbone, is often attenuated by poor cellular accumulation. In the present proof-of-concept study, we propose novel delivery system for asONs which implies modified so-called transport (tON), are oligodeoxyribonucleotides complementary to asON conjugated hydrophobic dodecyl moieties. Two types tONs, bearing at 5′-end up three residues attached through non-nucleotide inserts (TD series) or anchored...
Despite the proven tumorigenic effect of leptin on epithelial-derived cancers, its impact aggressiveness neural crest-derived notably neuroblastoma, remains largely unexplored. In our study, for first time, transcriptome analysis neuroblastoma tissue demonstrated that level is elevated in patients along with severity disease and inversely correlated patient survival. The treatment murine Neuro2a cells significantly stimulated their proliferation motility reduced cell adhesion, thus rendering...
In this study, we examined the in vivo toxicity of liposomes F consisting 1,26-bis(cholest-5-en-3-yloxycarbonylamino)-7,11,16,20-tetraazahexacosan tetrahydrochloride, lipid-helper 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine and folate lipoconjugate (O-{2-[rac-2,3-di(tetradecyloxy)prop-1-yloxycarbonyl]aminoethyl}-O’-[2-(pteroyl-L-glutam-5-yl)aminoethyl]octadecaethyleneglycol) investigated antitumor effect combined therapy MDR1-targeted siMDR/F complexes conventional polychemotherapy using...
Given the pharmacophore properties of nitrogen-containing moiety in molecular structure P-glycoprotein (P-gp) inhibitors, we report evaluation P-gp inhibitory and MDR reversal activities 2g, a 3-meta-pyridin-1,2,4-oxadiazole derivative 18βH-glycyrrhetinic acid. Through docking, have shown that 2g has potential to directly interact with transmembrane domain low free binding energy (−10.2 kcal/mol). Using KB-8-5 human cervical carcinoma cells RLS40 murine lymphosarcoma cells, both which...
Small membrane particles called extracellular vesicles (EVs) transport biologically active cargo between cells, providing intercellular communication. The clinical application of EVs is limited due to the lack scalable and cost-effective approaches for their production purification, as well effective loading strategies.
The objective of this study was to analyze the effects fluorophores on intracellular accumulation and biological activity small interfering RNA (siRNA) its cholesterol conjugates. In study, we used stem-loop real-time PCR calibration curves quantitate cellular siRNA accumulation. Attachment significantly affected both severity effect depended structure conjugate; (Cy5.5 or Alexa-488) attached siRNA, facing side duplex opposite cholesterol, enhanced unproductive conjugate when delivered in...
Cholesterol derivatives of nuclease-resistant, anti-MDR1 small-interfering RNAs were designed to contain a 2’-OMe-modified 21-bp siRNA and 63-bp TsiRNA in order investigate their accumulation silencing activity vitro vivo. The results showed that increasing the length RNA duplex such conjugate increases its biological when delivered using transfection agent. However, efficiency human drug-resistant KB-8-5 cells during delivery carrier-free mode was reduced as well target gene silencing....
We designed a multimeric nuclease-resistant 63-bp trimeric small-interfering RNA (tsiRNA) comprising in one duplex the sequence of siRNAs targeting mRNAs MDR1, LMP2, and LMP7 genes. show that such tsiRNA is able to suppress expression all target genes independently with high efficiency, acting via Dicer-dependent mechanism. diced into 42- 21-bp duplexes inside cell. tsiRNA-induced gene silencing characterized by kinetics similar canonical siRNA, while efficiency significantly higher than...
Conjugation of small interfering RNA (siRNA) with lipophilic molecules is one the most promising approaches for delivering siRNA in vivo. The rate molecular weight-dependent renal clearance critical efficiency this process. In study, we prepared cholesterol-containing supramolecular complexes containing from three to eight antisense strands and examined their accumulation silencing activity vitro We have shown first time that such 2′F, 2′OMe, LNA modifications exhibit both carrier-mediated...
A series of 1,2-, 1,4-disubstituted or 1,2,4-trisubstituted anthraquinone-based compounds was designed, synthesized, characterized and biologically evaluated for anticancer efficacy. 2- 4-arylated 1-hydroxy-9,10-antraquinones (anthracene-9,10-diones) were prepared by Suzuki–Miyaura cross-coupling reaction 1-hydroxy-2-bromoanthraquinone, 1-hydroxy-4-iodoanthraquinone 1-hydroxy-2,4-dibromoanthraquinone with arylboronic acids. The 2,4-dibromo-9,10-anthraquinone acids provide a convenient...
Small interfering RNA (siRNA) holds significant therapeutic potential by silencing target genes through interference. Current clinical applications of siRNA have been primarily limited to liver diseases, while achievements in delivery methods are expanding its various organs, including the lungs. Cholesterol-conjugated emerges as a promising approach due low toxicity and high efficiency. This study focuses on developing cholesterol-conjugated anti-Il6 evaluation potency for treatment...
Inflammatory diseases affect a substantial portion of the global population, and current treatment is not universally effective. We demonstrate that locally administered cholesterol-conjugated siRNA targeting Il6 alleviates symptoms acute lung injury, which makes it promising strategy for inflammatory with potential applications beyond lungs.
Cholesterol siRNA conjugates attract attention because they allow the delivery of into cells without use transfection agents. In this study, we compared efficacy and duration silencing induced by cholesterol selectively totally modified siRNAs their heteroduplexes same sequence explored impact linker length between 3' end sense strand on activity “light” “heavy” siRNAs. All 3'-cholesterol were equally active under transfection, but conjugate with a C3 was less than those...