|
- 现金
- 62111 元
- 精华
- 26
- 帖子
- 30437
- 注册时间
- 2009-10-5
- 最后登录
- 2022-12-28
|
平凡之路123 发表于 2019-12-31 22:22 
回复 乙肝人1949 的帖子
你不觉得REP就是个扯淡的药吗？问世十多年了，刚发现药物的作用机制，当初分子结 ...
REP2139 is a type of ON(oligonucleotide), just like RNAi. If you don't know the history of ON, please try to learn and not guess incorrectly.
就像RNAi一样，REP2139是一种ON（寡核苷酸）。如果您不知道开启的历史，请尝试学习，不要误猜.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4554547/#s001title
“治疗性ON的历史表明，这种新型分子药物在临床上具有许多潜在的应用。与其他新领域一样，从早期发现到此类疗法进入人体研究都存在一个滞后阶段。由于存在截然不同的模式作为TLRs和适体的配体，即反义，滞后阶段可能会因一种应用程序而异于另一种应用程序，这一点不足为奇，例如快速将siRNA引入临床试验就是例证。基于ON的疗法是使用相同的合成核苷酸化学方法，例如硫代磷酸酯修饰。主要是通过取代和修饰磷酸盐和碳水化合物来改变的骨架，而碱基通常对应于那些天然存在的，（L）-核糖核酸除外。
在本文中，我们仅简要介绍了递送方面，这仍然是一个重要的障碍，因为ON是相当大的实体，不会通过扩散进入细胞。最近在其他地方对不同的给药方法进行了综述。86,148然而，尽管细胞吸收仍然是一个限制，但很显然，几种化合物已经产生了显着的治疗效果。总体而言，这对于该领域而言是个好兆头，我们预测，这种发展可能会持续下去，不仅是针对肝脏内的靶标，而且还可能是为了校正例如骨髓细胞和中枢神经系统内的调节基因。这将实现最初的概念性梦想，即与低分子“传统”药物和生物制剂相比，ON药物在设计和开发上都更加直接。”
"The history of therapeutic ONs demonstrates that this new class of molecular medicines has numerous potential applications in the clinic. Similar to other novel fields, there is a lag phase from the early discoveries until such therapies enter into human studies. Given the highly different modes of action, that is, antisense, as ligands for TLRs, and aptamers, it is not surprising that the lag phase may differ from one application to another, as exemplified by the rapid introduction of siRNAs into clinical trials. A common denominator for several of the ON-based therapeutics is the use of the same synthetic nucleotide chemistries, such as the phosphorothioate modification. In the main, it is the backbone that has been altered by replacing and modifying both the phosphate and the carbohydrate, whereas the bases normally correspond to those naturally occurring, an exception being the (L)-ribonucleic acids.
In this review, we have only briefly addressed the delivery aspect and this remains an important hurdle, since ONs are rather large entities and do not enter into cells by diffusion. Different delivery approaches have recently been reviewed elsewhere.86,148 However, while cellular uptake remains a limitation, it is also clear that several compounds already yield significant treatment effects. Collectively, this bodes well for the field, and we predict that the development is likely to continue, not only for targets within the liver, but also for correction of regulatory genes in, for example, bone marrow cells and within the CNS. This would fulfill the initial conceptual dream that ON medicines, compared to low molecular “traditional” drugs as well as to biologics, are much more straightforward to both design and develop." |
|
楼主: 平凡之路123
发表于 2019-12-31 23:55
