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Cyclic dinucleotides (CDNs) are critical adjuvants in antiviral vaccines and cancer immunotherapy, primarily through the activation of the cGAS-STING signaling pathway. Evaluating the immune responses triggered by CDNs is essential for the development of effective adjuvants. In this study, we performed a comparative transcriptome analysis to characterize the immune responses elicited by the recently identified nuclease-resistant Drosophila and bacterial CDN, 3'2'-cGAMP, in mammalian immune cells.

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Zinc finger CCCH containing 11A (ZC3H11A) is a stress-induced protein that is upregulated in various conditions such as heat shock and virus infection. It has also been reported to be upregulated in certain cancers. The aim of this study was to evaluate the feasibility of targeting ZC3H11A as a therapeutic approach for cancer treatment, using nuclease-resistant, affinity-enhanced antisense oligonucleotide (ASO).

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Visually predicting microRNA-regulated tumor metastasis by intracellularly 3D counting of fluorescent spots based on in situ growth of DNA flares.

J Adv Res

January 2023

Cancer Metastasis Alert and Prevention Center, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350108, China. Electronic address:

Introduction: MicroRNAs (miRNAs) have been revealed to be critical genetic regulators in various physiological processes and thus quantitative information on the expression level of critical miRNAs has important implications for the initiation and development of human diseases, including cancers.

Objectives: We herein develop three-dimensionally (3D) counting of intracellular fluorescent spots for accurately evaluating microRNA-21 (miRNA-21) expression in individual HeLa cells based on stimuli-activated in situ growth of optical DNA flares, grid-patterned DNA-protein hybrids (GDPHs).

Methods: Target miRNA is sequence-specifically detected down to 10 pM owing to efficient signal amplification.

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Functional nucleic acids can be evolved using cycles of selection and amplification, starting from diverse-sequence libraries, which are typically restricted to natural or partially-modified polymer chemistries. Here, we describe the efficient DNA-templated synthesis and reverse transcription of libraries entirely composed of serum nuclease resistant alternative nucleic acid chemistries validated in nucleic acid therapeutics; locked nucleic acid (LNA), 2'--methyl-RNA (2'OMe-RNA), or mixtures of the two. We evaluate yield and diversity of synthesised libraries and measure the aggregate error rate of a selection cycle.

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In the past few years, several drugs derived from nucleic acids have been approved for commercialization and many more are in clinical trials. The sensitivity of these molecules to nuclease digestion implies the need to exploit resistant non-natural nucleotides. Among all the possible modifications, the one concerning the internucleoside linkage is of particular interest.

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