GSK3228836研究进展总结

tim889

StephenW 发表于 2022-9-18 16:03
"就搞独裁不让人说话。" - 他们不让人说话?  领域专家的说话比你的更重.

连横纵坐标是啥意思都看不明白的人，的确只会这么说，完全在预料之中。 学术讨论突然蹦出这么句话，只能显示你的无知(没读过论文) and/or 无能(读不懂论文)。

StephenW

tim889 发表于 2022-9-19 07:49
谢谢分享。

我尊重John的观点。但毕竟也是他个人的观点。我同意看数据本身的确是挺好，而且一直都是好到 ...

"他总不可能说我们为了股价做了某些事。"  - Replicor 是私有的，没有上市，因此没有股价.

tim889

StephenW 发表于 2022-9-18 16:06
"他总不可能说我们为了股价做了某些事。"  - Replicor 是私有的，没有上市，因此没有股价. ...

哦哦，那我更改一下。为了融资，稳住投资人？我就是讲了一个可能性，你跟我来纠结这个没意思。有空还是把论文全文读一读

newchinabok

tim889 发表于 2022-9-19 07:59
跟你讲了你这样搞成篇复制黏贴没意思的。

哪篇paper哪个实验那张图证明了NA直接silence了transcription, ...

哈哈，sw老师和我一样，自己发的贴子不看或者跑马观花一看。但是论坛重要百分之5的贴子，我是反复读了，还收藏，打印来读

tim889

newchinabok 发表于 2022-9-18 16:32
哈哈，sw老师和我一样，自己发的贴子不看或者跑马观花一看。但是论坛重要百分之5的贴子，我是反复读了，还 ...

自己不看没关系，喜欢复制黏贴也是他的自由。但是他非得来跟我前言不搭后语的讨论，这又是什么癖好？老爷爷很可爱。哈哈哈

newchinabok

tim889 发表于 2022-9-19 13:18
自己不看没关系，喜欢复制黏贴也是他的自由。但是他非得来跟我前言不搭后语的讨论，这又是什么癖好？老爷 ...

学术论坛就是要论，一看你就是牛人，我们只好派我们的主力队员sw和你讨论了

StephenW

tim889 发表于 2022-9-19 06:13
所有研究科学家都相信Rep？

REP2139所有的original research都是由Replicor这家公司做的。也没有独立的 ...

Aligois 也在研究 NAP

Aligos Therapeutics, Inc., a clinical-stage biopharmaceutical company, focuses to develop novel therapeutics to address unmet medical needs in viral and liver diseases. Its lead drug candidate is ALG-010133, a s-antigen transport-inhibiting oligonucleotide polymer that is in Phase Ib clinical trial for the treatment of chronic hepatitis B (CHB); and ALG-000184, a capsid assembly modulator, which is in Phase I clinical trials to treat CHB. The company also develops ALG-020572, an antisense oligonucleotide to prevent HBsAg translation and secretion; and ALG-055009, a small molecule THR-ß agonist that is in the Phase 1a/1b for the treatment of non-alcoholic steatohepatitis(NASH). In addition, it develops siRNA drug candidate, ALG-125755, as well as ALG-125097 and ALG-125819, demonstrated potent inhibition of HBsAg release from HBV-infected cells. It has entered into license and collaboration agreements with Luxna Biotech Co., Ltd. to develop and commercialize products containing oligonucleotides targeting hepatitis B virus genome; Emory University to provide hepatitis B virus capsid assembly modulator technology; research, licensing, and commercialization agreement with Katholieke Universiteit Leuven to develop coronavirus protease inhibitors; and Merck to discover, research, optimize, and develop oligonucleotides directed against a NASH. The company was incorporated in 2018 and is headquartered in South San Francisco, California.

newchinabok

StephenW 发表于 2022-9-19 14:30
Aligois 也在研究 NAP

Aligos Therapeutics, Inc., a clinical-stage biopharmaceutical company, focus ...

aligois开始研究时，我看过和rep有区别。sw老师，你仔细研究一下

StephenW

newchinabok 发表于 2022-9-19 14:37
aligois开始研究时，我看过和rep有区别。sw老师，你仔细研究一下

是, 你是对的. ALG-010133因疗效低, 已停止.

根据 Replicor 的说法：
ALG-010133 是 Aligos 正在开发的核酸聚合物 (NAP)
疗法。该 NAP 是 NAP 的锁定核酸 (LNA) 修饰版本
REP 2165 [2] 以前由 Replicor Inc. 开发。LNA 修改被放弃
十多年前，在核酸聚合物 (NAP) 的开发过程中，
复制器。可以预见的是，ALG-010133 单药治疗伴随着大量注射
部位反应 [3] 并且在 400 毫克剂量的 HBV 感染患者中没有活性 [4]，
而主动 NAP（REP 2139 和 REP 2055）可达到 7 log10 IU/mL HBsAg
在相似剂量和给药持续时间的单药治疗中较基线减少 [5]。这
所有 LNA 修饰的 NAP 的开发都已停止 [4]。机制原因
对于 ALG-010133 的失败以及为什么 LNA 修改在早期被丢弃
最近详细介绍了 NAP 的发展[2]。 HBV LNA的开发
由于肝毒性，反义寡核苷酸 (ASO) ALG-020572 也已被取消 [6]，
本 ASO [2] 中使用的 LNA 修改的预期并发症。
According to Replicor:
ALG-010133 is a nucleic acid polymer (NAP) that was under development by Aligos
Therapeutics. This NAP is a locked nucleic acid (LNA)-modified version of the NAP
REP 2165 [2] previously developed by Replicor Inc. The LNA modification was abandoned
more than a decade ago during the development of nucleic acid polymers (NAPs) at
Replicor. Predictably, ALG-010133 monotherapy is accompanied by significant injection
site reactions [ 3 ] and has no activity in HBV infected patients at the 400 mg dose [ 4],
whereas active NAPs (REP 2139 and REP 2055) achieve up to 7 log10 IU/mL HBsAg
reduction from baseline with monotherapy at similar doses and dosing duration [ 5]. The
development of all LNA-modified NAPs has been halted [4]. The mechanistic reasons
for the failure for ALG-010133 and why the LNA modification was discarded early in the
development of NAPs have been recently detailed [2]. Development of the HBV LNA
antisense oligonucleotide (ASO) ALG-020572 has also been canceled due to hepatoxicity [6 ],
an expected complication of the LNA modification that was employed in this ASO [2].

锁定核酸 (LNA)是什么，我不懂. 我只知道 Replicor 的 NAP 不依赖于 NA 序列(sequence).

newchinabok

StephenW 发表于 2022-9-19 16:43
是, 你是对的. ALG-010133因疗效低, 已停止.

根据 Replicor 的说法：

rep先讲故事融资再上市，现在没有后续试验，因为没人投了，融不到资了。乐复能都是这故事，风投。马云，京东，等等，都是这个玩法，技术路线不对就是垃圾