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Search for "siRNA" in Full Text gives 30 result(s) in Beilstein Journal of Organic Chemistry.
Switchable molecular tweezers: design and applications
Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45
- release of siRNA or miRNA encapsulated within them into the solution in vitro and in vivo [21]. The closed conformation of 2 with parallel alkyl chains acts as a building block of the bilayer membrane and is packed together with other lipids. When the surrounding medium becomes acidic, the tweezers adopt
The role of chemistry in the success of oligonucleotides as therapeutics
Beilstein J. Org. Chem. 2022, 18, 197–199, doi:10.3762/bjoc.18.22
- nucleotides; siRNAs; RNA-targeting oligonucleotides (e.g., antisense, siRNA, and anti-miR) are widely explored as fundamental research tools and are gaining increasing promise as therapeutic agents, particularly against diseases of genetic origin. The idea of treating a disease by targeting the molecular
- double-stranded nucleotides, which are called short interfering RNA or “siRNA,” can target mRNA and prevent it from being translated to make proteins [2]. While the mechanism by which antisense oligonucleotides (single stranded oligonucleotide) and siRNA (short RNA duplexes) work are completely different
- antisense and siRNAs) to the liver. Currently, there are three siRNA-GalNAc conjugates approved by the FDA and many others are in late-stage clinical trials. The success of GalNAc-oligonucleotide conjugates highlights the power of therapeutic oligonucleotides in treating previously untreatable conditions
Cationic oligonucleotide derivatives and conjugates: A favorable approach for enhanced DNA and RNA targeting oligonucleotides
Beilstein J. Org. Chem. 2021, 17, 1828–1848, doi:10.3762/bjoc.17.125
- native ON. Additionally, compared to wild‐type ONs or siRNA, ASOs carrying three modifications resulted in an equal or higher downregulation of ICAM‐1 expression [76]. A large study including 2’-aminoethyl RNA (monomer 33) showed that two incorporations at the 3’-end of a 22-mer antisense strand of a
- siRNA had better eGFP gene silencing activity compared to the control siRNA with a single 2’-OMe RNA monomer near the 5’-end [77]. Conversion of the primary amine on the aminopropyl modification into a tertiary amine (monomer 36) and insertion four times in a 16-mer ON (two in the middle and one near
- 38 improved the silencing activity of a siRNA when incorporated into the passenger strand (in the eGFP assay mentioned above). However, a decrease in the silencing activity was observed when incorporated into the guide strand [77]. To design a 2’-O-MOE cationic analogue, the 2'-O-(2-(2-(N,N
Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications
Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116
Antiviral therapy in shrimp through plant virus VLP containing VP28 dsRNA against WSSV
Beilstein J. Org. Chem. 2021, 17, 1360–1373, doi:10.3762/bjoc.17.95
- free of virus. Discussion CCMV VLPs containing dsRNA were successfully synthesized to silence the WSSV VP28 protein expression. Here we used a 6:1 mass ratio of capsid protein to dsRNA, according to previous works for the encapsidation of ssRNA [42] and siRNA [32]. To our knowledge, this is the first
Beyond ribose and phosphate: Selected nucleic acid modifications for structure–function investigations and therapeutic applications
Beilstein J. Org. Chem. 2021, 17, 908–931, doi:10.3762/bjoc.17.76
- oligonucleotides that have been explored for gene silencing. Keywords: antisense; chemically modified oligonucleotides; crystallography; siRNA; structure; Introduction The natural nucleic acids sugar-phosphate backbone comes in two flavors, 2'-deoxyribose in DNA and ribose in RNA. However, this relative
- modifications provide improved resistance to degradation by exo- and endonucleases and they both affect protein binding [16][17]. Eight of the now approved 13 oligonucleotide drugs feature the PS modification in the backbone and all four approved siRNA therapeutics: ONPATTRO® (patisiran, 2018), GIVLAARI
- 0.2–0.8 °C in the thermal stability of RNA/DNA hybrid duplexes for each AM1 modification [11][78]. NMR structural studies have shown that the AM1 modification is well tolerated in an RNA duplex, with little effect on the global structure [79]. Furthermore, siRNA duplexes with amide modifications at
Enhanced target cell specificity and uptake of lipid nanoparticles using RNA aptamers and peptides
Beilstein J. Org. Chem. 2021, 17, 891–907, doi:10.3762/bjoc.17.75
- interfering RNA (siRNA), through a stick bridge motif, to deliver siRNAs into the respective target cells. The G-3 siRNA conjugate had the highest efficacy with 70% delivery into target T-cells, while the A-1 siRNA conjugate showed a 20% delivery into target gp160-expressing cells [34][35]. Thus, both
- this study, we employed lipid compositions and formulation procedures previously reported in literature [4]. Specifically, the cationic and ionizable DLin-MC3-DMA lipid is a constituent of the FDA-approved LNP-formulated siRNA drug Patisiran® for treatment of familial transthyretin amyloidosis [36][37
- ]. Clinical trial safety assessments of this formulation showed no liver toxicity and no immune stimulation, with ≈10% of trial participants experiencing mild to moderate adverse events upon administration [38]. It includes encapsulation of siRNA by a mixture of lipid components, such as an ionizable cationic
Fluorescent phosphorus dendrimers excited by two photons: synthesis, two-photon absorption properties and biological uses
Beilstein J. Org. Chem. 2019, 15, 2287–2303, doi:10.3762/bjoc.15.221
- at different time points after spinal cord injury. This dendrimer has potential uses as a drug/siRNA carrier and phenotype-specific cell tracer, i.e., for enhanced cell therapies combined with monitoring of cell fate and function [61]. Dendrimers with pyridine imine terminal functions and their
Oligonucleotide analogues with cationic backbone linkages
Beilstein J. Org. Chem. 2018, 14, 1293–1308, doi:10.3762/bjoc.14.111
- a specific protein, which leads to effective (though reversible) and selective downregulation of the protein's activity. A third option for the biological action of oligonucleotide structures is the triggering of the RNA interference mechanism by double-stranded 'small interfering' RNA (siRNA
Stimuli-responsive oligonucleotides in prodrug-based approaches for gene silencing
Beilstein J. Org. Chem. 2018, 14, 436–469, doi:10.3762/bjoc.14.32
- (2’-OMe), 2’-fluoro (2’-F), and 2’-O-(2-methoxyethyl) (MOE) [9][10]. Some examples of the combination of 2’-OMe and 2’-F modified nucleotides in siRNAs were reported, and the potency of the modified siRNA was increased compared to unmodified siRNA. Many chemical modifications have been introduced in
- ’-OH siRNAs was similarly demonstrated in the presence of 10 mM GSH. Furthermore, firefly luciferase expression in A549-Luc cells was inhibited by 2’-O-MDTM siRNAs to a higher extent than the unmodified siRNA regardless of the modification site (5’-end and/or the seed region of the antisense strand
- the 3’-end of the sense strand to prepare cholesterol-conjugated siRNAs that were efficiently delivered to rat oligodendrocytes in vivo and achieved significant specific gene knockdown in these cells (Scheme 4A) [19]. The comparison with a non-cleavable alkyl linker suggests that a lipophilic siRNA
Preparation of trinucleotide phosphoramidites as synthons for the synthesis of gene libraries
Beilstein J. Org. Chem. 2018, 14, 397–406, doi:10.3762/bjoc.14.28
- polystyrene support decorated with a photolabile linker and its potential use for the synthesis of siRNA duplexes under mild and neutral conditions [36]. A similar strategy was used for the synthesis of partially 2'/3'-O-acetylated RNA oligonucleotides [37]. A photo-cleavable linker would also have potential
The chemistry and biology of mycolactones
Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159
- accompanied by macroscopic or ultrastructural signs of nerve destruction and hypoesthesia. Subsequent experiments revealed that mycolactone exposure caused hyperpolarization of neurons derived from PC12 cells that was mediated by the TRAAK potassium channel. Finally, screening of a siRNA library targeting
Glyco-gold nanoparticles: synthesis and applications
Beilstein J. Org. Chem. 2017, 13, 1008–1021, doi:10.3762/bjoc.13.100
- titers of specific IgG antibodies towards type 14 polysaccharide compared with GAuNP exclusively displaying Pn14. The GAuNP technology has also been applied in the regulation of important genes of the apoptotic pathway. New GAuNP systems displaying cMyc targeting siRNA resulted capable of inducing
A postsynthetically 2’-“clickable” uridine with arabino configuration and its application for fluorescent labeling and imaging of DNA
Beilstein J. Org. Chem. 2017, 13, 127–137, doi:10.3762/bjoc.13.16
- traffic lights” [17][19][25] that are energy transfer-based nucleic acid probes that can be used in molecular beacons [26], especially for vesicular microRNA imaging in living cancer cells [27], and for siRNA transport imaging [28]. Donor and acceptor dyes are combined in an interstrand and diagonal
Efficient mechanochemical synthesis of regioselective persubstituted cyclodextrins
Beilstein J. Org. Chem. 2016, 12, 2364–2371, doi:10.3762/bjoc.12.230
- millimolar scale, they are easily scalable. Keywords: green chemistry; nucleophilic substitution; planetary ball mill; siRNA delivery intermediate; sugammadex; Introduction Cyclodextrins (CDs) are cyclic α(1→4)glucopyranosides and have been fully described in a number of publications [1][2][3]. They are
- -CD derivatives are used in siRNA delivery and gene therapy [6]. The alkyl chain, usually C10–C16, makes the product very amphiphilic, which means that it is difficult to purify not only from possible byproducts but also from the reagents. Additionally, sulfur-containing organic compounds can form
- protonated product during the filtration, the complete elimination of an organic solvent could be achieved. Yields can be improved further at even larger scales. The encouraging results with MPA led us to an attempt to simplify the synthesis of an intermediate of a promising candidate for siRNA delivery. The
Organic chemistry meets polymers, nanoscience, therapeutics and diagnostics
Beilstein J. Org. Chem. 2016, 12, 1638–1646, doi:10.3762/bjoc.12.161
- when we demonstrated very efficient DNA transfection (i.e., gene delivery) using gold nanoparticles [55]. In later work we improved on our gene delivery vehicles [56], demonstrated the delivery of siRNA [57] and enzymes [58] using nanoparticle assemblies. All of these systems (as well as essentially
- made use of the oil interior of the capsule to provide dual protein (caspase 3) and therapeutic (paclitaxel) delivery where the two payloads worked synergistically for chemotherapy [65]. Being supramolecular types, we figured we could swap out the anionic proteins used above for anionic siRNA [66]. In
- this case we were right – we can deliver siRNA directly into the cytosol with great efficiency [67]. Concurrent with our delivery efforts, we were working on ways to track nanoparticles in living systems. Back in 2008 I had a student working jointly with Richard Vachet, and I suggested the rather crazy
Synthesis of a deuterated probe for the confocal Raman microscopy imaging of squalenoyl nanomedicines
Beilstein J. Org. Chem. 2016, 12, 1127–1135, doi:10.3762/bjoc.12.109
- was extended to other nucleoside analogues such as antiretroviral agents, ddC, ddI and AZT [14] and to siRNA oligonucleotides [15]. More notably, squalenoylation of adenosine and the subsequent formation of NAs, allowed prolonged circulation of this nucleoside, providing neuroprotection in mice with
Size-controlled and redox-responsive supramolecular nanoparticles
Beilstein J. Org. Chem. 2015, 11, 2388–2399, doi:10.3762/bjoc.11.260
- . Davis et al. showed the formation of SNPs using attractive electrostatic interactions between positively charged β-cyclodextrin (CD)-containing polymers and negatively charged siRNA at the core [8]. Neutral adamantyl-grafted poly(ethylene glycol) (Ad-PEG) was incorporated at the surface to stabilize
Preparation of a disulfide-linked precipitative soluble support for solution-phase synthesis of trimeric oligodeoxyribonucleotide 3´-(2-chlorophenylphosphate) building blocks
Beilstein J. Org. Chem. 2015, 11, 1553–1560, doi:10.3762/bjoc.11.171
- acids have been used to regulate gene expression through different mechanisms of action, such as antisense oligonucleotides [1][2], ribozymes [3], interfering RNAs (siRNA) [4][5] and immunostimulatory CpG [6] based therapeutics. At the same time, the interest in detailed understanding of the factors
Terminal lipophilization of a unique DNA dodecamer by various nucleolipid headgroups: Their incorporation into artificial lipid bilayers and hydrodynamic properties
Beilstein J. Org. Chem. 2015, 11, 913–929, doi:10.3762/bjoc.11.103
- complex nanoarchitectures [33][34], the interaction of such nanostructures with lipid membranes [35][36][37][38], as well as the optimization of the in vivo delivery of lipophilic siRNA [10][11][12] (e.g., by DNA trafficking [7]). Further studies from our group will include the binding of terminally
Multivalency as a chemical organization and action principle
Beilstein J. Org. Chem. 2015, 11, 848–849, doi:10.3762/bjoc.11.94
- ], peptide–polymer interactions [17][18][19][20] tripodal-catecholates [21] and polycatechol–surface interactions [22] as well as multivalent organocatalyts [23]. Finally, multivalent dendritic poly(arginine/histidine)-siRNA complexes are evaluated regarding their transfection efficiency [24]. In the future
Multivalent dendritic polyglycerolamine with arginine and histidine end groups for efficient siRNA transfection
Beilstein J. Org. Chem. 2015, 11, 763–772, doi:10.3762/bjoc.11.86
- -2025, USA 10.3762/bjoc.11.86 Abstract The success of siRNA-based therapeutics highly depends on a safe and efficient delivery of siRNA into the cytosol. In this study, we post-modified the primary amines on dendritic polyglycerolamine (dPG-NH2) with different ratios of two relevant amino acids, namely
- , arginine (Arg) and histidine (His). To investigate the effects from introducing Arg and His to dPG, the resulting polyplexes of amino acid functionalized dPG-NH2s (AAdPGs)/siRNA were evaluated regarding cytotoxicity, transfection efficiency, and cellular uptake. Among AAdPGs, an optimal vector with (1:3
- ) Arg to His ratio, showed efficient siRNA transfection with minimal cytotoxicity (cell viability ≥ 90%) in NIH 3T3 cells line. We also demonstrated that the cytotoxicity of dPG-NH2 decreased as a result of amino acid functionalization. While the incorporation of both cationic (Arg) and pH-responsive
Exploring monovalent and multivalent peptides for the inhibition of FBP21-tWW
Beilstein J. Org. Chem. 2015, 11, 701–706, doi:10.3762/bjoc.11.80
- release of the dendritic polymer into the cytoplasm [13]. These polymeric scaffolds have been explored well for tumor targeting by using polymer-drug conjugates or polyplexes with genes or siRNA [14], but also have the potential to inhibit protein–protein interaction in cells, by displaying multiple
Formation of nanoparticles by cooperative inclusion between (S)-camptothecin-modified dextrans and β-cyclodextrin polymers
Beilstein J. Org. Chem. 2015, 11, 147–154, doi:10.3762/bjoc.11.14
- as nanoparticles and micelles. Recently, the first delivery of siRNA in humans using CD polymers was reported [14] and currently two drug-delivery systems based on CD polymers have entered clinical phase II trials in cancer treatment [6]. The advantages of CD polymers can be exploited in preparation
Synthesis of a resin monomer-soluble polyrotaxane crosslinker containing cleavable end groups
Beilstein J. Org. Chem. 2014, 10, 2623–2629, doi:10.3762/bjoc.10.274
- PRXs with cleavable disulfide end groups can form stable complexes with negatively charged biomacromolecules such as proteins, pDNA, or siRNA [11][12][13][14][15]. These PRX–biomolecule complexes were successfully delivered into the cytoplasm, and the biomolecules were effectively released after the
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