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Chimeric RNA Oligonucleotides with Triazole and Phosphate Linkages: Synthesis and RNA Interference
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Dr. Tomoko Fujino Kanako Kogashi Koudai Okada Dr. Martin Mattarella Takeru Suzuki Dr. Kenichi Yasumoto Prof. Kazuhiro Sogawa Prof. Hiroyuki Isobe 《化学:亚洲杂志》2015,10(12):2683-2688
Chimeric RNA oligonucleotides with an artificial triazole linker were synthesized using solution‐phase click chemistry and solid‐phase automated synthesis. Scalable synthesis methods for jointing units for the chimeric structure have been developed, and after click‐coupling of the jointing units with triazole linkers, a series of chimeric oligonucleotides was prepared by utilizing the well‐established phosphoramidite method for the elongation. The series of chimeric 21‐mer oligonucleotides that possessed the triazole linker at different strands and positions allowed for a screening study of the RNA interference to clarify the preference of the triazole modifications in small‐interfering RNA molecules. 相似文献
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Inside Cover: Chimeric RNA Oligonucleotides with Triazole and Phosphate Linkages: Synthesis and RNA Interference (Chem. Asian J. 12/2015)
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Although image-based phenotypic assays are considered a powerful tool for siRNA library screening, the reproducibility and biological implications of various image-based assays are not well-characterized in a systematic manner. Here, we compared the resolution of high throughput assays of image-based cell count and typical cell viability measures for cancer samples. It was found that the optimal plating density of cells was important to obtain maximal resolution in both types of assays. In general, cell counting provided better resolution than the cell viability measure in diverse batches of siRNAs. In addition to cell count, diverse image-based measures were simultaneously collected from a single screening and showed good reproducibility in repetitions. They were classified into a few functional categories according to biological process, based on the differential patterns of hit (i.e., siRNAs) prioritization from the same screening data. The presented systematic analyses of image-based parameters provide new insight to a multitude of applications and better biological interpretation of high content cell-based assays. 相似文献
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Kohzoh IMAI Hiroaki TANIGUCHI 《Proceedings of the Japan Academy. Series B, Physical and biological sciences》2022,98(7):325
PRDI-BF1 and RIZ (PR) domain zinc finger protein 14 (PRDM14), first reported in 2007 to be overexpressed in breast cancer, plays an important role in breast cancer proliferation. Subsequent studies reported that PRDM14 is expressed in embryonic stem cells, primordial germ cells, and various cancers. PRDM14 was reported to confer stemness properties to cancer cells. These properties induce cancer initiation, cancer progression, therapeutic resistance, distant metastasis, and recurrence in refractory tumors. Therefore, PRDM14 may be an ideal therapeutic target for various types of tumors. Silencing PRDM14 expression using PRDM14-specific siRNA delivered through an innovative intravenous drug delivery system reduced the size of inoculated tumors, incidence of distant metastases, and increased overall survival in nude mice without causing adverse effects. Therapeutic siRNA targeting PRDM14 is now being evaluated in a human phase I clinical trial for patients with refractory breast cancer, including triple-negative breast cancer. 相似文献
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With its nearly unrestricted possibilities, gene therapy attracts more and more significance in modern-day research. The only issue still seeming to hold back its clinical success is the actual effective delivery of genetic material. Nucleic acids are in general challenging to administer to their intracellular targets because of their unfavorable pharmaceutical characteristics. Polymeric nanogels present a promising delivery platform for oligonucleotide-based therapies, as the growing number of reports deliberated in this review represents. Within the scope of this article, recent progress in the use of nanogels as gene delivery vectors is summarized and different examples of modified, stimuli-responsive, targeted, and codelivering nanogels are discussed in detail. Furthermore, major aspects of successful gene delivery are addressed and critically debated in regard to nanogels, giving insights into what progress has been made and which key issues still need to be further approached. 相似文献
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Aviram Avital Noy Sadot Muzika Zohar Persky Gili Bar Yuval Michaeli Yulia Fridman Avishai Karny Jeny Shklover Janna Shainsky Sigal Savaldi-Goldstein Haim Weissman Oded Shoseyov Avi Schroeder 《Advanced functional materials》2021,31(44):2101003
Grapevine leafroll disease (GLD) is a globally spreading viral infection that causes major economic losses by reducing crop yield, plant longevity, and berry quality, with no effective treatment. Grapevine leafroll associated virus-3 (GLRaV-3) is the most severe, prevalent GLD strain affecting wine production. Here, the ability of RNA interference (RNAi), a non-GMO gene-silencing pathway, to treat GLRaV-3 in infected Cabernet Sauvignon grapevines is evaluated. Lipid-modified polyethylenimine (lmPEI) is synthesized as the carrier for long double-stranded RNA (dsRNA, 250-bp-long) that targets RNA polymerase and coat protein is a gene target that are conserved in the GLRaV-3 genome. Self-assembled dsRNA–lmPEI particles, 220 nm in diameter, display inner ordered domains spaced 7.3 ± 2 nm from one another, correlating to lmPEI wrapping spirally around the dsRNA. The particles effectively protect RNA from degradation by ribonucleases and show to increase uptake rate into plant cells as a result of the lipid component comprising the RNA carrier. In three field experiments, a single dose of foliar sprayed treatment of the RNA-particles knocks down GLRaV-3 titer, and multiple doses of the treatment keep the viral titer at baseline and trigger recovery of the vine and berries. This study demonstrates RNAi as a promising platform for treating viral diseases in agriculture. 相似文献
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Supramolecular Self‐Assembly of Histidine‐Capped‐Dialkoxy‐Anthracene: A Visible‐Light‐Triggered Platform for Facile siRNA Delivery
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Shahad Alsaiari Kholod Alamoudi Dr. Aws Alshamsan Dr. Abdulaziz AlMalik Dr. Karim Adil Prof. Mohamed Eddaoudi Prof. Niveen M. Khashab 《Chemistry (Weinheim an der Bergstrasse, Germany)》2016,22(39):13789-13793
Supramolecular self‐assembly of histidine‐capped‐dialkoxy‐anthracene (HDA) results in the formation of light‐responsive nanostructures. Single‐crystal X‐ray diffraction analysis of HDA shows two types of hydrogen bonding. The first hydrogen bond is established between the imidazole moieties while the second involves the oxygen atom of one amide group and the hydrogen atom of a second amide group. When protonated in acidic aqueous media, HDA successfully complexes siRNA yielding spherical nanostructures. This biocompatible platform controllably delivers siRNA with high efficacy upon visible‐light irradiation leading up to 90 % of gene silencing in live cells. 相似文献