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Blocking Translation of Oncogenic mRNA

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

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Synthesis and Properties of D-Thymidylyl (3'→5')L-Thymidine (D/L-TpT)

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Chinese Chemical Letters 1999年第9期10卷 741-744页

作者： Xiao Hui GU Yi Bing ZHANG Yao Quan CHEN(State Key Laboratory of Bio-organic and Natural Products Chemistry, Shanghai Instituteof Organic Chemistry, Chinese Academy of Sciences. 354 Fenglin Road. Shanghai 200032) State Key Lab. Bio-Organ. Nat. P. Shanghai Inst. of Organic Chemistry Chinese Academy of Sciences 354 Fenglin Road Shanghai 200032 China

The synthesis and properties of D-thymidylyl (3'→5')L-thymidine (D/L-TpT) aredescribed.

关键词： antisense oligonucleotides anticancer synthesis D-thymidylyl (3'→5')L-thymidine.

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The Possibility of Nucleic Acids to Act as Anti-Viral Therapeutic Agents—A Review

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Open Journal of Medical Microbiology 2021年第3期11卷 198-248页

作者： Md. Selim Reza Farzana Mim Mohammad Rezaul Quader Mohammad Jahidur Rahman Khan Md. Sabir Hossain Kazi Rasel Uddin Salina Akter Sharmin Rahman Sumon Roy Md. Abdullah Rumman RT-PCR LAB Bangabandhu Sheikh Mujib Medical College Faridpur Bangladesh Department of Biochemistry and Molecular Biology Jahangirnagar University Dhaka Bangladesh Department of Biochemistry Bangabandhu Sheikh Mujib Medical College Faridpur Bangladesh Department of Microbiology Shaheed Suhrawardy Medical College Dhaka Bangladesh Department of Pharmacology Ibrahim Medical College Dhaka Bangladesh

For just about 30 years, researchers have considered the likelihood to utilize nucleic acids as antiviral therapeutics. In principle, small single-stranded nucleotide sequence (oligonucleotide) could hybridize to a particular gene or messenger RNA and diminish transcription or translation, respectively, in this manner decreasing the amount of protein that is synthesized. Until now, an incredible number of antisense oligonucleotides, double-stranded oligonucleotides, aptamers, ribozymes, deoxyribozymes, interfering RNAs, chimeric RNA-DNA molecules, antibody genes has been created artificially and applied effectively for comprehension and manipulating biological processes and in clinical preliminaries to treat a variety of diseases. Their versatility and potency make them similarly fit candidates for fighting viral infections. However, troubles with their efficiency, off-target effects, toxicity, delivery, and stability halted the development of nucleic acid-based therapeutics that can be utilized in the clinic. The potential for nucleic acid therapeutic agents is significant and is quite recently beginning to be realized. In this review, we have summarized some of the recent advancements made in the area of nucleic acid based therapeutics and focused on the methods of their delivery and associated challenges.

关键词： antisense oligonucleotides Aptamers Ribozymes Deoxyribozymes RNA Interference

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CD133/Prominin-1反义寡核苷酸对人肝癌细胞系Huh7体外生长特性的影响

CD133/Prominin-1反义寡核苷酸对人肝癌细胞系Huh7体外生长特性的...

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湖北省抗癌协会青年委员会成立大会暨第一届青年学术论坛

作者：姚杰曹文淼刘伟任精华张涛解放军161医院华中科技大学同济医学院附属协和医院肿瘤中心

目的探讨肝癌肿瘤干细胞(CSCs)表面标记物,5次跨膜蛋白CD133(又名Prominin-1)的功能可否影响人肝癌细胞Huh7的体外生长特性,并分析其同家族蛋白Prominin2是否有与之类似或协同的功能。方法采用脂质体介导CD133/Prominin-1反义寡核苷酸(A... 详细信息

目的探讨肝癌肿瘤干细胞(CSCs)表面标记物,5次跨膜蛋白CD133(又名Prominin-1)的功能可否影响人肝癌细胞Huh7的体外生长特性,并分析其同家族蛋白Prominin2是否有与之类似或协同的功能。方法采用脂质体介导CD133/Prominin-1反义寡核苷酸(ASODN)及无关寡核苷酸(NSODN)分别转染入两组Huh7人肝癌细胞,以未处理细胞为空白对照。转染后各组细胞采用RT-PCR检测CD133/Prominin-1 mRNA水平,流式细胞仪检测CD133表达,细胞集落形成实验检测细胞集落形成能力,流式细胞仪检测细胞周期分布。重复转染实验,并加设Prominin-2 ASODN转染组、半量CD133/Prominin-1 ASDON+半量Prominin-2 ASODN联合转染组,转染后检测各组细胞集落形成能力。结果CD133/Prominin-1 ASDON组细胞与空白对照及NSODN组相比,其CD133/Prominin-1 mRNA水平,细胞表面CD133表达率均明显降低(P0.05)。而Prominin-2 ASODN组细胞集落形成率较对照组无显著性差异(P>0.05)。结论ASODN转染下调CD133/Prominin-1表达可使Huh7细胞的集落形成能力显著下降,且可对Huh7细胞周期的整体分布产生一定影响。而Prominin-2 ASODN转染对Huh7细胞集落形成能力无显著影响。

关键词： Cancer stem cells CD133/Prominin-1 Liver neoplasms antisense oligonucleotides

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Self-assembled Double Bundle DNA Tetrahedron for Efficient antisense Delivery

Self-assembled Double Bundle DNA Tetrahedron for Efficient A...

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第十一届全国化学生物学学术会议

作者： Xiaohui Wu Juanjuan yang Jianbing Liu Baoquan Ding CAS Key Laboratory of Nanosystem and Hierarchical Fabrication CAS Center for Excellence in NanoscienceNational Center for Nanoscience and Technology

Addressable and programmable DNA nanostructures are promising biomaterials to arrange multiple functional components for efficient and site-specific drug delivery. Herein,we report a double bundle DNA tetrahedron(invented by Mao et al ) rationally designed for delivery of antisense oligonucleotides silencing proto-oncogene c-raf.The antisense strands are located at the inside surface of the DNA tetrahedron to decrease the access of DNA digestive enzymes.Functionalized with nuclear targeting peptides,the DNA tetrahedron can be internalized by A549 cells and assists the delivery of antisense oligonucleotides towards the nucleus to increase the chance to down-regulate target mRNA in nucleus and cytoplasm.antisense strands released from the tetrahedron in response to the intracellular reducing environment can inhibit cell proliferation at a low concentration without transfection reagent.Finally,efficient knockdown of c-raf gene is observed,which verified our design.This designed DNA-based nanocarrier system will open a new avenue for efficient delivery of nucleic acid drugs.

关键词： Double bundle DNA tetrahedron antisense oligonucleotides Drug delivery Cancer therapy

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Expression of heparanase mRNA in esophageal cancer cells

Expression of heparanase mRNA in esophageal cancer cells

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中国首届国际食管癌学术会议暨第七届全国食管癌学术会议

作者： Kui - Sheng Chen Lan Zhang Lin TangYun - Han Zhang Dong - ling Gao Liang Yan Lei ZhangDepartment of Pathology, the First Affiliated Hospital, ZhengzhouUniversity Key Laboratory of Henan Tumor Pathology

＜正＞ AIM: To investigate the effects of antisense oligonucleotides （ ASODNs） on mRNA expression of heparanase in human esophageal cancer EC9706 cells. METHODS: One non - sense oligonu-cleotide （ N - ODN） and five ASODNs against different heparanase mRNA sites were transfected into EC9706 cells, then the expression of heparanase mRNA in EC9706 cells was studied by in situ hybridization. RESULTS: The expression of heparanase mRNA could be inhibited by ASODNs. There was no significant difference among five ASODNs （ P ＞ 0. 05） , but there was a significant difference between ASODNs and N - ODN or non - transfected group （ASODN1: 2. 25±0. 25, ASODN2: 2. 21±0. 23, ASODN3: 2. 23±0.23 , ASODN4: 2. 25±0. 24 vs N - ODN: 3.47±2. 80 or non - transfected group: 3.51±2.93 respectively, P＜0.05）. CONCLUSION: The expression of heparanase mRNA in EC9706 cells can be inhibited by ASODNs in vivo, and heparanase ASODNs can inhibit metastasis of esophageal squmous cell carcinoma or other tumors by inhibiting the expression of heparanase.

关键词： Esophageal cancer EC9706 cells Heparanase antisense oligonucleotides In situ hybridization

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