将RNA Aptamer转化为修改后的DNA Aptamers提供了长时间的稳定性和增强的抗瘤活性
Paola Amero1, Ganesh L R Lokesh2, Rajan R Chaudhari1
1Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, United States.
Journal of the American Chemical Society
|May 14, 2021
概括
针对酸-AXL的修饰DNA合体显示出更好的稳定性和生物可用性,提供了有前途的治疗方法. 在临床前的模型中,这些瘤有效地减少了瘤的生长和转移.
科学领域:
- 生物化学
- 分子生物学
- 药理学
背景情况:
- 由于副作用最小,阿普塔默是类似抗体的寡核酸,具有治疗潜力.
- 在临床应用中,aptamer的稳定性和生物可用性仍然存在挑战.
- -AXL是各种癌症的标,包括卵巢癌.
研究的目的:
- 开发针对基-AXL的改性DNA合体,以提高稳定性和生物可用性.
- 评估这些修饰的aptamer的体外和体外疗效.
- 建立基于aptamer的治疗方法的临床转化基础.
主要方法:
- 转换RNA体为向酸-AXL的修饰DNA体
- 对17个修饰DNA的候选aptamer进行比较分析.
- 化学修饰包括骨干硫酸/二硫酸和5'-端聚乙烯糖醇结合.
- 在卵巢癌正型小鼠模型中的体外和体内评估.
主要成果:
- 选择的aptamer候选物GLB- G25和GLB- A04显示出优异的生物可用性和稳定性.
- 修改后的阿普坦体表现出最佳的药理动力学,减少核酶水解和清.
- 在体内观察到瘤生长和转移的显著减少.
- 在低剂量时,可以实现高且持续的酸-AXL抑制.
结论:
- 通过化学修饰,可以显著提高它们的稳定性和生物可用性.
- 在临床前的卵巢癌模型中,针对酸-AXL的修饰性受体显示出强烈的抗瘤作用.
- 这些发现支持修改后的aptamer和伴随生物标志物的临床转化.
更多相关视频
09:04Sequence-specific and Selective Recognition of Double-stranded RNAs over Single-stranded RNAs by Chemically Modified Peptide Nucleic Acids
Published on: September 21, 2017
9.7K
06:02Determining the Thermodynamic and Kinetic Association of a DNA Aptamer and Tetracycline Using Isothermal Titration Calorimetry
Published on: August 23, 2022
3.2K
相关概念视频
RNA Stability
34.4K
Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...
34.4K
Types of RNA
70.1K
Overview
Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in the regulation of gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA...
Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in the regulation of gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA...
70.1K
Transfer RNA Synthesis
12.5K
One of the unique features of tRNA is the presence of modified bases. In some tRNAs, modified bases account for nearly 20% of the total bases in the molecule. Altogether, these unusual bases protect the tRNA from enzymatic degradation by RNases.
Each of these chemical modifications is carried by a specific enzyme, post-transcription. All of these enzymes have unique base and site-specificity. Methylation, the most common chemical modification, is carried by at least nine different enzymes, with...
Each of these chemical modifications is carried by a specific enzyme, post-transcription. All of these enzymes have unique base and site-specificity. Methylation, the most common chemical modification, is carried by at least nine different enzymes, with...
12.5K
Experimental RNAi
6.7K
RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
6.7K
Riboswitches
8.9K
Riboswitches are non-coding mRNA domains that regulate the transcription and translation of downstream genes without the help of proteins. Riboswitches bind directly to a metabolite and can form unique stem-loop or hairpin structures in response to the amount of the metabolite present. They have two distinct regions – a metabolite-binding aptamer and an expression platform.
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
8.9K
