A5043128490- RNA Interference and Gene Delivery
- Advanced biosensing and bioanalysis techniques
- DNA and Nucleic Acid Chemistry
- MicroRNA in disease regulation
- interferon and immune responses
- Immunotherapy and Immune Responses
- RNA and protein synthesis mechanisms
- Immune Response and Inflammation
- Virus-based gene therapy research
- RNA Research and Splicing
- CRISPR and Genetic Engineering
- Metal complexes synthesis and properties
- Computational Drug Discovery Methods
- RNA regulation and disease
- Cholinesterase and Neurodegenerative Diseases
- Extracellular vesicles in disease
- Origins and Evolution of Life
- Cancer-related molecular mechanisms research
- Pesticide Exposure and Toxicity
- Neonatal Respiratory Health Research
- Bone fractures and treatments
- Monoclonal and Polyclonal Antibodies Research
- Genomics and Chromatin Dynamics
- Lymphoma Diagnosis and Treatment
- Chemical Synthesis and Analysis
Siberian Branch of the Russian Academy of Sciences
2014-2024
Institute of Chemical Biology and Fundamental Medicine
2014-2024
Russian Academy of Sciences
1998-2011
Engelhardt Institute of Molecular Biology
2009
Institute of Bioorganic Chemistry
1989-2003
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,...
Small interfering RNAs (siRNAs) are considered as potent agents for specific gene silencing; however, nuclease sensitivity of siRNA limits their biomedical applications. Till date, no universal methodology has been developed to improve the resistance siRNA, preserving low toxicity and high activity. In this study, we proposed an algorithm site-specific modification siRNAs based on mapping nuclease-sensitive sites in presence serum followed by incorporation 2′-O-methyl analogs ribonucleotides...
Short nuclear regulatory RNAs play a key role in the main stages of maturation precursors major RNA species. Small (snRNAs) form core spliceosome and are responsible for splicing pre-mRNA molecules. nucleolar (snoRNAs) direct post-transcriptional modification pre-rRNAs. A promising strategy development non-coding (ncRNAs) mimicking molecules is introduction modified nucleotides, which normally present natural ncRNAs, into structure synthetic RNAs. We have created set snoRNAs snRNA analogs...
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...
Small interfering RNAs (siRNA) are able to activate the mammalian innate immune system depending on their structure, sequence, and method of delivery. The immunostimulatory activity double-stranded RNA can be applied antiviral antitumor therapy. Here we identified a set 19-bp duplexes with 3-nucleotid overhangs in 3′ ends that display immunostimulating (here after RNA, or isRNA) studied sequence/activity relationships. It was found introduction substitutions middle part isRNA sequence (10–16...
In this study, the impact of different delivery systems on cytokine-inducing, antiproliferative, and antitumor activities short immunostimulatory double-stranded RNA (isRNA) was investigated. The systems, consisting polycationic amphiphile 1,26-bis(cholest-5-en-3-yloxycarbonylamino)-7,11,16,20 tetraazahexacosan tetrahydrochloride (2X3), lipid-helper dioleoylphosphatidylethanolamine (DOPE), were equipped with polyethylene glycol lipoconjugates differing in molecular weight structure. main...
Small interfering RNAs, depending on their structure, delivery system and sequence, can stimulate innate adaptive immunity. The aim of this study was to investigate the antitumor antimetastatic effects immunostimulatory 19-bp dsRNA with 3'- trinucleotide overhangs (isRNA) melanoma B16 in C57Bl/6 mice. Recently developed novel cationic liposomes 2X3-DOPE were used for vivo isRNA. Administration isRNA/2X3-DOPE complexes significantly inhibits tumor growth metastasis. Histopathological analysis...
After decades of nonspecific lymphoma therapy, personalized approaches such as described here are on the horizon.
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide with limited therapeutic options. Since HCC has been shown to be immunogenic, immunotherapy considered a promising approach. Small interfering RNAs (siRNAs), depending on their structure and sequence, can trigger innate immune system, which potentially enhance adaptive anticancer response in tumor-bearing subjects. Immunostimulatory properties nucleic acids applied develop adjuvants for treatment. The...
The thermodynamic asymmetry of siRNA duplexes determines their silencing activity. Favorable can be achieved by incorporation mismatches into the 3' part sense strand, providing fork-siRNAs, which exhibit higher activity and sensitivity to nucleases. Recently, we found that selective 2'-O-methyl modifications nuclease-sensitive sites significantly improve its nuclease resistance without substantial loss Here, examined impact nucleotide number location on anti-MDR1 siRNAs. We both nonmodified...
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...
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...
Previously, we described a 19-base pair double-stranded RNA with 3'-trinucleotide overhangs, acting as immunostimulatory (isRNA). This molecule demonstrated notable antiproliferative effects on cancer cells, inhibited tumor growth, and elicited antiviral responses by inducing cytokine interferon production. Within this study, compared the efficiency of lung fibrosis development, initiated in mice BLM or LPS using different schemes induction. Then effect isRNA used preventive...
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-
Inhibition of p-glycoprotein (PGP) expression and reverse multidrug resistance (MDR) phenotype in KB-8-5 cells by synthetic 21-bp double-stranded oligoribonucleotides were investigated. siRNA constructs for the efficient down regulation MDR1 that are active nanomolar concentrations cause reversal MDR developed.
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...