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https://www.readbyqxmd.com/read/28938163/tumor-cell-targeted-delivery-of-crispr-cas9-by-aptamer-functionalized-lipopolymer-for-therapeutic-genome-editing-of-vegfa-in-osteosarcoma
#1
Chao Liang, Fangfei Li, Luyao Wang, Zong-Kang Zhang, Chao Wang, Bing He, Jie Li, Zhihao Chen, Atik Badshah Shaikh, Jin Liu, Xiaohao Wu, Songlin Peng, Lei Dang, Baosheng Guo, Xiaojuan He, D W T Au, Cheng Lu, Hailong Zhu, Bao-Ting Zhang, Aiping Lu, Ge Zhang
Osteosarcoma (OS) is a highly aggressive pediatric cancer, characterized by frequent lung metastasis and pathologic bone destruction. Vascular endothelial growth factor A (VEGFA), highly expressed in OS, not only contributes to angiogenesis within the tumor microenvironment via paracrine stimulation of vascular endothelial cells, but also acts as an autocrine survival factor for tumor cell themselves, thus making it a promising therapeutic target for OS. CRISPR/Cas9 is a versatile genome editing technology and holds tremendous promise for cancer treatment...
September 13, 2017: Biomaterials
https://www.readbyqxmd.com/read/28938065/in-vitro-selection-of-diversely-functionalized-aptamers
#2
Dehui Kong, Wayland Yeung, Ryan Hili
We describe the application of T4 DNA ligase-catalyzed DNA templated oligonucleotide polymerization toward the evolution of a diversely functionalized nucleic acid aptamer for human α-thrombin. Using a 256-membered ANNNN co-monomer library comprising 16 sub-libraries modi-fied with different functional groups, a highly-functionalized aptamer for thrombin was raised with a dissociation constant of 1.6 nM. The aptamer was found to be selective for thrombin, and re-quired the modifications for binding affinity...
September 22, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28937998/selection-of-dna-aptamers-specific-for-live-pseudomonas-aeruginosa
#3
Jennifer Soundy, Darren Day
Pseudomonas aeruginosa is an opportunistic pathogen that causes significant morbidity and mortality in immunocompromised patients, particular cystic fibrosis sufferers, burns victims, diabetics and neonates. It thrives in moist places where it forms biofilms that are exceedingly difficult to eradicate on hospital surfaces, in water supplies and implanted biomaterials. Using a live cell SELEX approach we selected DNA aptamers to P. aeruginosa grown as biofilms in microfluidic cells. From a pool of aptamer candidates showing tight binding a stem-loop structure was identified as being important for binding...
2017: PloS One
https://www.readbyqxmd.com/read/28935443/complex-formation-with-protamine-prolongs-the-thrombin-inhibiting-effect-of-dna-aptamer-in-vivo
#4
V A Spiridonova, T M Novikova, D M Nikulina, T A Shishkina, E V Golubkina, O S Dyukareva, N N Trizno
Antithrombin DNA aptamersRE31 are single-chain oligonucleotides that fold into three-dimensional forms allowing them to bind the enzyme with high affinity and inhibit its activity in vivo. They are rapidly degraded by a nonspecific nuclease, and, to prolong the lifetime of the aptamer DNA in the bloodstream, it is necessary to coat it with a polymer envelope. A new approach to solving this problem based on preparation of DNA-polyelectrolyte complexes with a minimal particle size that can circulate with blood flow...
September 18, 2017: Biochimie
https://www.readbyqxmd.com/read/28934318/identification-of-lag3-high-affinity-aptamers-by-ht-selex-and-conserved-motif-accumulation-cma
#5
Mario Martínez Soldevilla, Sandra Hervas, Helena Villanueva, Teresa Lozano, Obdulia Rabal, Julen Oyarzabal, Juan José Lasarte, Maurizio Bendandi, Susana Inoges, Ascensión López-Díaz de Cerio, Fernando Pastor
LAG3 receptor belongs to a family of immune-checkpoints expressed in T lymphocytes and other cells of the immune system. It plays an important role as a rheostat of the immune response. Focus on this receptor as a potential therapeutic target in cancer immunotherapy has been underscored after the success of other immune-checkpoint blockade strategies in clinical trials. LAG3 showcases the interest in the field of autoimmunity as several studies show that LAG3-targeting antibodies can also be used for the treatment of autoimmune diseases...
2017: PloS One
https://www.readbyqxmd.com/read/28931278/fluorescence-resonance-energy-transfer-based-dna-nanoprism-with-a-split-aptamer-for-atp-sensing-in-living-cells
#6
Xiaofang Zheng, Ruizi Peng, Xi Jiang, Yaya Wang, Shuai Xu, Guoliang Ke, Ting Fu, Qiaoling Liu, Shuang-Yan Huan, Xiaobing Zhang
We have developed a DNA nanoprobe for adenosine triphosphate (ATP) sensing in living cells, based on the split aptamer and the DNA triangular prism (TP). In which nucleic acid aptamer was split into two fragments, the stem of the split aptamer was respectively labeled donor and acceptor fluorophores that underwent an fluorescence resonance energy transfer if two ATP molecules were bound as target molecule to the recognition module. Hence, ATP as a target induced the self-assembly of split aptamer fragments and thereby brought the dual fluorophores into close proximity for high FRET efficiency...
September 21, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28930315/mapping-the-interaction-sites-of-mucin-1-and-dna-aptamer-by-atomic-force-microscopy
#7
Nan Wang, Miaomiao Zhang, Xuejuan Chen, Xingxing Ma, Chen Li, Zhe Zhang, Jilin Tang
Mucin 1 (MUC1) is an attractive tumor marker for cancer diagnosis. An advanced atomic force microscopy (AFM) mode, peak-force tapping AFM with an aptamer functionalized tip, was introduced to map the specific interaction sites of an aptamer and MUC1. Single molecular force spectroscopy (SMFS) was used to investigate dynamic parameters of the aptamer-MUC1.
September 20, 2017: Analyst
https://www.readbyqxmd.com/read/28929744/optimizing-stem-length-to-improve-ligand-selectivity-in-a-structure-switching-cocaine-binding-aptamer
#8
Miguel A D Neves, Aron A Shoara, Oren Reinstein, Okty Abbasi Borhani, Taylor R Martin, Philip E Johnson
Understanding how aptamer structure and function are related is crucial in the design and development of aptamer-based biosensors. We have analysed a series of cocaine-binding aptamers with different lengths of their stem 1 in order to understand the role that this stem plays in the ligand-induced structure-switching binding mechanism utilized in many of the sensor applications of this aptamer. In the cocaine-binding aptamer the length of stem 1 controls whether the structure-switching binding mechanism for this aptamer occurs or not...
September 20, 2017: ACS Sensors
https://www.readbyqxmd.com/read/28929743/the-design-of-a-dual-channel-self-reference-photoelectrochemical-biosensor
#9
Nan Hao, Ying Zhang, Hui Zhong, Zhou Zhou, Rong Hua, Jing Qian, Qian Liu, Henan Li, Kun Wang
Photoelectrochemical (PEC) biosensors are usually based on the single photocurrent change caused by biorecognition events between analytes and probes. However, the photocurrent may be influenced by other factors besides target analytes and bring a false result. To improve the accuracy and reliability of PEC detection, here we proposed the design of a dual channel self-reference PEC biosensors. CdTe and CdTe-graphene oxide (GO) were chosen as the two PEC active material and modified onto two adjacent areas on the ITO electrode...
September 20, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28929739/ultrasensitive-capture-detection-and-release-of-circulating-tumor-cells-using-nanochannel-ionchannel-hybrid-coupled-with-electrochemical-detection-technique
#10
Jing Cao, Xiao-Ping Zhao, Muhammad Rizwan Younis, Zhong-Qiu Li, Xing-Hua Xia, Chen Wang
With the growing demands of the early, accurate, and sensitive diagnosis for cancers, the development of new diagnostic technologies becomes increasingly important. In this study, we proposed a strategy for efficient capture and sensitive detection of circulating tumor cells (CTCs) using array nanochannel-ionchannel hybrid coupled with electrochemical detection technique. The aptamer probe was immobilized on the ionchannel surface to couple with the protein overexpressed on CTCs membrane. Through this special molecular recognition, CTCs can be selectively captured...
September 20, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28929152/size-dependent-targeted-delivery-of-gold-nanoparticles-modified-with-the-il-6r-specific-aptamer-air-3a-to-il-6r-carrying-cells
#11
Lisa Prisner, Nadine Bohn, Ulrich Hahn, Alf Mews
The delivery of gold nanoparticles (AuNPs) to specific cells strongly depends on the properties e.g. the size of the particles and is of great interest for a large variety of biomedical applications. Here we investigated the size dependence of the receptor-ligand mediated AuNP delivery to cells by comparing very small "molecular" Au-clusters of only 2 nm to larger 7 nm and 36 nm AuNPs with a distinct surface plasmon resonance. Since the molecular weight in this range changes by almost three orders of magnitude, we show how the amount of gold relates to the number of delivered AuNPs...
September 20, 2017: Nanoscale
https://www.readbyqxmd.com/read/28928437/as1411-aptamer-anionic-linear-globular-dendrimer-g2-iohexol-selective-nano-theranostics
#12
Pardis Mohammadzadeh, Reza Ahangari Cohan, Seyedeh Masoumeh Ghoreishi, Ahmad Bitarafan-Rajabi, Mehdi Shafiee Ardestani
Molecular theranostics is of the utmost interest for diagnosis as well as treatment of different malignancies. In the present study, anionic linear globular dendrimer G2 is employed as a suitable carrier for delivery and AS1411 aptamer is exploited as the targeting agent to carry Iohexol specifically to the human breast cancer cells (MCF-7). Dendrimer G2 was prepared and conjugation of dendrimer and aptamer was carried out thereafter. Based on the data yielded by AFM, morphology of smooth and spherical non-targeted dendrimer changed to the rough aspherical shape when it conjugated...
September 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28925689/highly-efficient-capture-and-electrochemical-release-of-circulating-tumor-cells-by-using-aptamers-modified-gold-nanowire-arrays
#13
Ting-Ting Zhai, Dekai Ye, Qian-Wen Zhang, Zeng-Qiang Wu, Xing-Hua Xia
The effectively capturing and releasing of circulating tumor cells (CTCs) is of significant importance in cancer prognose and treatment. Herein, we report a highly efficient method to capture and release human leukemic lymphoblasts (CCRF-CEM) using aptamers modified gold nanowire arrays (AuNWs). The gold nanowires, showing tunable morphologies from relatively random pillar deposit to uniform arrays, were fabricated by electrochemical deposition using anodic aluminum oxide (AAO) as template. Upon simply modification with aptamers by Au-S chemistry, the uniform AuNWs exhibit higher specificity to target cells...
September 19, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28924154/a-dna-aptamer-efficiently-inhibits-the-infectivity-of-bovine-herpesvirus-1-by-blocking-viral-entry
#14
Jian Xu, Xixi Zhang, Shuanghai Zhou, Junjun Shen, Dawei Yang, Jing Wu, Xiaoyang Li, Meiling Li, Xiufen Huang, Joshua E Sealy, Munir Iqbal, Yongqing Li
Bovine herpesvirus 1 (BoHV-1) is an important pathogen of domestic and wild cattle responsible for major economic losses in dairy and beef industries throughout the world. Inhibition of viral entry plays a crucial role in the control of BoHV-1 infection and aptamers have been reported to inhibit viral replication. In this study, nine DNA aptamers that target BoHV-1 were generated using systemic evolution of ligands by exponential enrichment. Of the nine candidates, aptamer IBRV-A4 exhibited the highest affinity and specificity for BoHV-1, which bound to BoHV-1 with a Kd value of 3...
September 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28921494/solid-phase-synthesis-of-rna-analogs-containing-phosphorodithioate-linkages
#15
Xianbin Yang
The oligoribonucleotide phosphorodithioate (PS2-RNA) modification uses two sulfur atoms to replace two non-bridging oxygen atoms at an internucleotide phosphorodiester backbone linkage. Like a natural phosphodiester RNA backbone linkage, a PS2-modified backbone linkage is achiral at phosphorus. PS2-RNAs are highly stable to nucleases and several in vitro assays have demonstrated their biological activity. For example, PS2-RNAs silenced mRNA in vitro and bound to protein targets in the form of PS2-aptamers (thioaptamers)...
September 18, 2017: Current Protocols in Nucleic Acid Chemistry
https://www.readbyqxmd.com/read/28918528/signaling-of-the-complement-cleavage-product-anaphylatoxin-c5a-through-c5ar-cd88-contributes-to-pharmacological-hematopoietic-stem-cell-mobilization
#16
Kamila Bujko, Sylwia Rzeszotek, Kai Hoehlig, Jun Yan, Axel Vater, Mariusz Z Ratajczak
Several mechanisms have been postulated for orchestrating the mobilization of hematopoietic stem/progenitor cells (HSPCs), and we previously proposed that activation of the complement cascade plays a crucial role in the initiation and execution of the egress of HSPCs from bone marrow (BM) into peripheral blood (PB). In support of this notion, we demonstrated that mice deficient in the mannan-binding lectin (MBL) pathway, which activates the proximal part of the complement cascade, as well as mice deficient in the fifth component of the complement cascade (C5), which is part of the distal part of the complement cascade, are poor mobilizers...
September 16, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/28918052/a-ctla-4-antagonizing-dna-aptamer-with-antitumor-effect
#17
Bo-Tsang Huang, Wei-Yun Lai, Yi-Chung Chang, Jen-Wei Wang, Shauh-Der Yeh, Emily Pei-Ying Lin, Pan-Chyr Yang
The successful translation of cytotoxic T lymphocyte antigen-4 (CTLA-4) blockade has revolutionized the concept of cancer immunotherapy. Although monoclonal antibody therapeutics remain the mainstream in clinical practice, aptamers are synthetic oligonucleotides that encompass antibody-mimicking functions. Here, we report a novel high-affinity CTLA-4-antagonizing DNA aptamer (dissociation constant, 11.84 nM), aptCTLA-4, which was identified by cell-based SELEX and high-throughput sequencing. aptCTLA-4 is relatively stable in serum, promotes lymphocyte proliferation, and inhibits tumor growth in cell and animal models...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28918021/in%C3%A2-vitro-selection-of-cell-internalizing-dna-aptamers-in-a-model-system-of-inflammatory-kidney-disease
#18
Glory Ranches, Melanie Lukasser, Herbert Schramek, Andreas Ploner, Taras Stasyk, Gert Mayer, Günter Mayer, Alexander Hüttenhofer
Chronic kidney disease (CKD) is a progressive pathological condition marked by a gradual loss of kidney function. Treatment of CKD is most effective when diagnosed at an early stage and patients are still asymptomatic. However, current diagnostic biomarkers (e.g., serum creatinine and urine albumin) are insufficient for prediction of the pathogenesis of the disease. To address this need, we applied a cell-SELEX (systematic evolution of ligands by exponential enrichment) approach and identified a series of DNA aptamers, which exhibit high affinity and selectivity for cytokine-stimulated cells, resembling some aspects of a CKD phenotype...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28918019/dual-tumor-targeting-nanocarrier-system-for-sirna-delivery-based-on-prna-and-modified-chitosan
#19
Lin Li, Xiaoqin Hu, Min Zhang, Siyu Ma, Fanglin Yu, Shiqing Zhao, Nan Liu, Zhiyuan Wang, Yu Wang, Hua Guan, Xiujie Pan, Yue Gao, Yue Zhang, Yan Liu, Yang Yang, Xuemei Tang, Mingyuan Li, Cheng Liu, Zhiping Li, Xingguo Mei
Highly specific and efficient delivery of siRNA is still unsatisfactory. Herein, a dual tumor-targeting siRNA delivery system combining pRNA dimers with chitosan nanoparticles (CNPPs) was designed to improve the specificity and efficiency of siRNA delivery. In this dual delivery system, folate-conjugated and PEGylated chitosan nanoparticles encapsulating pRNA dimers were used as the first class of delivery system and would selectively deliver intact pRNA dimers near or into target cells. pRNA dimers simultaneously carrying siRNA and targeting aptamer, the second class of delivery system, would specifically deliver siRNA into the target cells via aptamer-mediated endocytosis or proper particle size...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28917799/a-reagentless-and-reusable-electrochemical-aptamer-based-sensor-for-rapid-detection-of-ampicillin-in-complex-samples
#20
Zhi-Gang Yu, Rebecca Y Lai
We report the design and fabrication of a "signal-on" electrochemical aptamer-based (E-AB) sensor for detection of ampicillin. The signaling of the sensor is based on target binding-induced changes in the conformation and flexibility of the methylene blue-modified aptamer probe. The sensor's response is fast; signal saturation can be reached in ~ 200s. Since all the sensor components are surface-immobilized, it is regenerable and can be reused for at least three times. It has demonstrated good specificity and is capable of differentiating between ampicillin and structurally similar antibiotics such as amoxicillin...
January 1, 2018: Talanta
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