GalNAc-siRNA conjugates represent a truly novel class of RNA therapeutics enabling liver hepatocyte-specific delivery of small-interfering RNA (siRNA) payloads at an unprecedented level of efficacy. In vitro, and also in vivo,GalNAc conjugated multivalent siRNA is more potent than siRNA alone and th...
而siRNA因为其本身容易降解,所以目前多采用载体递送技术。目前进入临床的相关药物主要是Alnylam公司研发的GalNAc-siRNA药物,包括Givlaari、inclisiran与lumasiran等,均是利用了GalNAc与ASGPR的高亲和力,从而提高其靶向性[3](表1)。 表1:进入临床的GalNAc修饰的siRNA药物[3] 在当前的基因治疗领域,尽管基因编辑疗法备受瞩目...
Delivery of Oligonucleotides to the Liver with GalNAc: From Researchto Registered Therapeutic Drug. Mol Ther. 2020 Aug 5;28(8):1759-1771. 4.Springer AD, Dowdy SF. GalNAc-siRNA Conjugates:Leading the Way for Delivery of RNAi Therapeutics. Nucleic Acid Ther. 2018Jun;28(3):109-118....
ASGPR是一种数量众多的异源低聚物的内吞型受体,只存在于肝脏实质细胞,能特异性地识别并结合GalNAc。 GalNAc与肝脏实质细胞表面的ASGPR结合后,通过细胞内吞作用,进入到细胞内形成内涵体,从而将足够数量的siRNA带入细胞内,诱导选择性RNA沉默反应。GalNAc递送途径只在ASGPR表达的肝脏细胞上有效,其他细胞/组织中尚无有效的...
“pathway” of diseases, therefore “interfering” with gene transcription. But for these siRNA to reach the target mRNA, they must be precisely and efficiently delivered to the tissue where the mRNA are converted to proteins. Alnylam scientists have pioneered the use of LNPs and conjugates for ...
如您需要查看完整版(目录+图表)或申请报告样本可点击链接:https://www.qyresearch.com.cn/reports/4391508/galnac-sirna-conjugates-drug GalNAc-siRNA 药物报告主要研究企业名单如下,也可根据客户要求增加目标企业:苏州瑞博生物、圣诺制药、Alnylam Pharmaceuticals、Arrowhead、诺和诺德、Silence Therapeutics、Arbutus、诺华、...
您需要查看完整报告目录或了解相关报告问题可以联系我们,也可以点击链接:https://www.yhresearch.cn/reports/2078997/galnac-sirna-conjugates 本文调研和分析全球GalNAc-siRNA 缀合物发展现状及未来趋势,核心内容如下: (1)全球GalNAc-siRNA 缀合物市场总体概览: ...
Arrowhead的Dynamic PolyConjugates(DPC™),是另一款将siRNA递送至肝细胞的递送系统。DPC™递送平台的核心特征是含有丁基氨乙烯基醚的聚合物PBAVE(polymer composed of butyl and amino vinyl ether)。 PBAVE具有感应内涵体/溶酶体pH而促进逃逸的能力,GalNAc修饰的PBAVE可通过二硫键与siRNA偶联形成DPC™-siRNA...
Review of GalNAc-siRNA Conjugates Across Multiple Programs Demonstrates No Evidence of Thrombocytopenia or Pro-inflammatory EffectsCoagulation dysfunction, predominantly mediated by thrombocytopenia and immunostimulatory effects, including complement activation, has been associated with a number of oligonucleotides ...
Taken together, the evidence that we have presented points towards RNAi-mediated, hybridization-based off-target effects driven by the seed region of the antisense strand as the major cause for the rat hepatotoxicity observed with a random subset of hepatotoxic GalNAc-siRNA conjugates. This is furth...