- Synthesis, gene-silencing activity and nuclease resistance of 3′-3′-linked double short hairpin RNA
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To improve the nuclease resistance of siRNA while reducing its induction of an innate immune response and maintaining its biological activity for possible therapeutic application, we designed and synthesized a series of double short hairpin RNAs (dshRNAs)
- Masuda, Hirofumi,Watanabe, Naoki,Naruoka, Haruna,Nagata, Seigo,Takagaki, Kazuchika,Wada, Takeshi,Yano, Junichi
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- Disulfide-Unit Conjugation Enables Ultrafast Cytosolic Internalization of Antisense DNA and siRNA
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Development of intracellular delivery methods for antisense DNA and siRNA is important. Previously reported methods using liposomes or receptor-ligands take several hours or more to deliver oligonucleotides to the cytoplasm due to their retention in endosomes. Oligonucleotides modified with low molecular weight disulfide units at a terminus reach the cytoplasm 10 minutes after administration to cultured cells. This rapid cytoplasmic internalization of disulfide-modified oligonucleotides suggests the existence of an uptake pathway other than endocytosis. Mechanistic analysis revealed that the modified oligonucleotides are efficiently internalized into the cytoplasm through disulfide exchange reactions with the thiol groups on the cellular surface. This approach solves several critical problems with the currently available methods for enhancing cellular uptake of oligonucleotides and may be an effective approach in the medicinal application of antisense DNA and siRNA.
- Shu, Zhaoma,Tanaka, Iku,Ota, Azumi,Fushihara, Daichi,Abe, Naoko,Kawaguchi, Saki,Nakamoto, Kosuke,Tomoike, Fumiaki,Tada, Seiichi,Ito, Yoshihiro,Kimura, Yasuaki,Abe, Hiroshi
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- Synthesis of non-natural sequence-encoded polymers using phosphoramidite chemistry
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Sequence-defined non-natural polyphosphates were prepared using iterative phosphoramidite protocols on a polystyrene solid support. Three monomers were used in this work: 2-cyanoethyl (3-dimethoxytrityloxy-propyl) diisopropylphosphoramidite (0), 2-cyanoethyl (3-dimethoxytrityloxy-2,2-dimethyl-propyl) diisopropylphosphoramidite (1), and 2-cyanoethyl (3-dimethoxytrityloxy-2,2-dipropargyl-propyl) diisopropylphosphoramidite (1′). Phosphoramidite coupling steps allowed rapid synthesis of homopolymers and copolymers. In particular, the comonomers (0, 1), (0, 1′), and (1, 1′) were used to synthesize sequence-encoded copolymers. It was found that long encoded sequences could be easily built using phosphoramidite chemistry. ESI-HRMS, MALDI-HRMS, NMR, and size exclusion chromatography analyses indicated the formation of monodisperse polymers with controlled comonomer sequences. The polymers obtained with the comonomers (0, 1′) and (1, 1′) were also modified by copper-catalyzed azide-alkyne cycloaddition with a model azide compound, namely 11-azido-3,6,9-trioxaundecan-1-amine. 1H and 13C NMR analysis evidenced quantitative modification of the alkyne side-chains of the monodisperse copolymers. Thus, the molecular structure of the coding monomer units can be easily varied after polymerization. Altogether, the present results open up interesting avenues for the design of information-containing macromolecules.
- Al Ouahabi, Abdelaziz,Charles, Laurence,Lutz, Jean-Fran?ois
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- Enzymatic combinatorial nucleoside deletion scanning mutagenesis of functional RNA
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We describe a general and simple method to identify catalytically and structurally important nucleotides in functional RNAs. Our approach is based on statistical replacement of each nucleoside with a non-nucleosidic spacer (C3 linker, Δ), followed by sepa
- Wawrzyniak-Turek, Katarzyna,H?bartner, Claudia
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- Short optimally capped duplex DNA as conformationally restricted analogue of B-DNA
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We describe the synthesis of short double-stranded DNA fragments (see 4 and 13) which are capped on both ends by an optimally designed linker molecule. The new structures are stable with respect to hybrid dissociation and should have implications in physical studies involving double-stranded DNA as well as in the antisense area for the specific modulation of gene expressions.
- Bannwarth,Dorn,Iaiza,Pannekouke
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- RNA interference agent, method for producing same, and use therefor
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Provided is an RNA interference agent, with which a suppression effect on the off-target effect can be obtained with a simple system. The disclosures relate to an RNA interference agent provided with a single-stranded oligonucleotide passenger strand having one or two or more PAZ domain low-affinity units at the 3′-end.
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(2018/07/15)
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- Oligophosphates with an antiviral action
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Novel oligophosphates with an antiviral action of the formula STR1 in which n is 3-50, B and E are, independently of one another, O, S or NH, A is O, NR or S, D is O, S or NR2, in which independently each R is H, alkyl, aralkyl or aryl, and
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