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PEGylation of therapeutic oligonucletides： From linear to highly branched PEG architectures

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Nano Research 2018年第10期11卷 5519-5534页

作者： Xueguang Lu Ke Zhang Department of Chemistry and Chemical Biology Northeastern University Boston Massachusetts 02115 USA

PEGylation, the attachment of poly（ethylene glycol）（PEG）, has been adopted to improve the pharmacokinetic properties of oligonucleotide therapeutics for nearly 30 years. Prior efforts mainly focused on the investigation of linear or slightly branched PEG having different molecular weights, terminal functional groups, and possible oligonucleotide sites for functionalization. Recent studies on highly branched PEG （including brush, star, and micellar structures） indicate superior properties in several areas including cellular uptake, gene regulation efficac~ reduction of side effects, and biodistribution. This review focuses on comparing the effects of PEG architecture on the physiochemical and biological properties of the PEGylated oligonucleotide.

关键词： PEGylation oligonucleotide brush polymer antisense small interfering RNA aptamer phosphorothioate

Engineering Novel Molecular Beacon Constructs to Study Intracellular RNA Dynamics and Localization

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Genomics, Proteomics & Bioinformatics 2017年第5期15卷 279-286页

作者： Zhao Ma Xiaotian Wu Christopher J.Krueger Antony K.Chen Department of Biomedical Engineering College of Engineering Peking University Beijing 100871 China Wallace H Coulter Department of Biomedical Engineering Georgia Institute of Technology Atlanta GA 30332 USA

With numerous advancements in novel biochemical techniques, our knowledge of the role of RNAs in the regulation of cellular physiology and pathology has grown significantly over the past several decades. Nevertheless, detailed information regarding RNA processing, trafficking, and localization in living cells has been lacking due to technical limitations in imaging single RNA transcripts in living cells with high spatial and temporal resolution. In this review, we discuss tech- niques that have shown great promise for single RNA imaging, followed by highlights in our recent work in the development of molecular beacons （MBs）, a class of nanoscale oligonucleotide-probes, for detecting individual RNA transcripts in living cells. With further refinement of MB design and development of more sophisticated fluorescence microscopy techniques, we envision that MB-based approaches could promote new discoveries of RNA functions and activities.

关键词： Y-O-methyl RNA phosphorothioate Molecular beacon RNA dynamics Single-molecule RNAimaging

Blocking Translation of Oncogenic mRNA

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Journal of Cancer Therapy 2023年第6期14卷 233-256页

作者： Kelvin N. Christie Long Island University Post Campus Brookville USA

Double-stranded RNA-mediated interference (RNAi), antisense oligonucleotides (ASO), and ribozymes have excellent specificity to their target oncogenic mRNA. They also seem to show great promise when it comes to treating cancer. The problem is that RNAi, ASO, and ribozymes have poor stability and are constantly being degraded by nucleases. Researchers have made some efforts to increase antisense oligonucleotides’ stability by creating phospharimidate and phosphorothioate. Currently, ribozymes, antisense oligonucleotides, and (RNAi) are the three main methods used to target RNA. These methods are currently undergoing clinical trials for the purpose of focusing on specific RNAs involved in disorders like cancer and neurodegeneration. In fact, ASOs that target amyotrophic lateral sclerosis and spinal muscular atrophy have produced promising results in clinical trials. The formation of chemical alterations that boost affinity and selectivity while reducing noxiousness owing to off-target impacts are two benefits of ASOs. Another benefit is increased affinity. With a focus on RNAi and ASOs, this review illustrated the main therapeutic strategies of RNA therapy now in use.

关键词： Antisense Oligonucleotides Ribozymes phosphorothioate Double-Stranded RNA-Mediated Interference Nucleases

Depletion of telomerase RNA inhibits growth of gastrointestinal tumors transplanted in mice

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World Journal of Gastroenterology 2013年第15期19卷 2340-2347页

作者： Xue-Cheng Sun Jing-Yi Yan Xiao-Lei Chen Ying-Peng Huang Xian Shen Xiao-Hua Ye Department of Gastroenterology and Hepatology the First Affiliated Hospital of Wenzhou Medical College Department of Gastroenterology and General Surgery the First Affiliated Hospital of Wenzhou Medical College

AIM: To explore effects of telomerase RNA-targeting phosphorothioate antisense oligodeoxynucleotides (PS-ASODN) on growth of human gastrointestinal stromal tumors transplanted in mice. METHODS: A SCID mouse model for transplantation of human gastrointestinal stromal tumors (GISTs) was established using tumor cells from a patient who was diagnosed with GIST and consequently had been treated with imatinib. GIST cells cultured for 10 passages were used for inoculation into mice. Transfection of PS-ASODN was carried out with Lipotap Liposomal Transfection Reagent. GISTs that subsequently developed in SCID mice were subjected to intratumoral injection once daily from day 7 to day 28 postinoculation, and mice were divided into the following four groups according to treatment: PS-ASODN group (5.00 μmoL/L of oligonucleotide, each mouse received 0.2 mL once daily); imatinib group (0.1 mg/g body weight); liposome negative control group (0.01 mL/g); and saline group (0.01 mL/g). On day 28, the mice were sacrificed, and tumor attributes including weight and longest and shortest diameters were measured. Tumor growth was compared between treatment groups, and telomerase activity was measured by enzyme-linked immunosorbent assay. Apoptosis was examined by flow cytometry. Real-time polymerase chain reaction was used to detect expression of the mRNA encoding the apoptosis inhibition B-cell leukemia/lymphoma 2 (bcl-2 ) gene. RESULTS: In the PS-ASODN group, tumor growth was inhibited by 59.437%, which was markedly higher than in the imatinib group (11.071%) and liposome negative control group (2.759%) [tumor inhibition=(mean tumor weight of control group - mean tumor weight of treatment group)/(mean tumor weight of control group) × 100%]. Telomerase activity was significantly lower (P < 0.01) in the PS-ASODN group (0.689 ± 0.158) compared with the imatinib group (1.838 ± 0.241), liposome negative control group (2.013 ± 0.273), and saline group (2.004 ± 0.163). Flow cytometry revealed that the apoptosis rate of tumor cells treated w

关键词： Gastrointestinal stromal tumor phosphorothioate antisense oligonucleotides Imatinib Tumor inhibitory rate Telomerase activity

化学改造短链核酸用于“精准”生物传感及基因调控（英文）

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化学改造短链核酸用于“精准”生物传感及基因调控（英文）

第十一届全国化学生物学学术会议

作者： Chunmei Gu Lu Xiao Mengli Feng Jiachen Shang 向宇 Department of Chemistry Tsinghua University 清华大学

Oligonucleotides are useful tools in chemical biology for biosensing and therapeutics.The well-known examples include functional nucleic acids(aptamers and DNAzymes/ribozymes)

关键词： Oligonucleotide phosphorothioate Reactive Oxygen Speices DNAzyme siRNA

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硫代寡核苷酸的FT-ICR-MS分析

分析测试学报 2008年第S1期27卷 15-,18页

作者：刘锋赵永强王娜何昆军事医学科学院国家生物医学分析中心北京100850

The phosphorothioate oligonucleotides are used more and more for cancer treatment.Fast analysis of phosphorothioate oligonucleotide is important for quality control of this drug.In this paper,FT-ICR-MS was used to analyze a phosphorothioate oligonucleotide with 6 321 u.Experimental results showed that accurate relative molecular mass of phosphorothioate oligonucleotide determined by FT-ICR-MS can be used for confirmation of its composition.

关键词： phosphorothioate oligonucleotide FT-ICR-MS analysis