Abstract：
UNASSIGNED: Liver fibrosis represents an unmet medical condition with growing incidence and only limited therapeutic options. Interfering with dysregulated gene expression was considered a specific treatment approach, and we are here reviewing the current options to modulate transcription and translation with small molecule inhibitors of involved enzymes, transcription factors or by using non-coding RNA molecules (RNA interference) or DNA antisense oligonucleotides. Despite promising results in preclinical models, only limited data are available from studies in humans.
UNASSIGNED: This expert opinion provides a general overview of how to interfere with gene expression (transcription and translation) and highlighting recent achievements in liver fibrosis.
UNASSIGNED: Many compounds that were explored to modulate gene expression in liver fibrosis (models) were developed as anti-cancer agents. Their use in humans with impaired liver function is often impaired by the lack of specificity to inhibit only fibrosis-related genes in the liver and by associated general toxicity and narrow therapeutic windows. RNAi approaches show a higher degree of specificity and potentially less systemic toxicity. Clinical development in liver fibrosis requires close interaction between pharmaceutical companies and regulatory authorities to address topics like relevant (surrogate) endpoints to achieve meaningful readouts faster.
UNASSIGNED: This expert opinion provides a general overview of how to interfere with gene expression (transcription and translation) and highlighting recent achievements in liver fibrosis.
UNASSIGNED: Many compounds that were explored to modulate gene expression in liver fibrosis (models) were developed as anti-cancer agents. Their use in humans with impaired liver function is often impaired by the lack of specificity to inhibit only fibrosis-related genes in the liver and by associated general toxicity and narrow therapeutic windows. RNAi approaches show a higher degree of specificity and potentially less systemic toxicity. Clinical development in liver fibrosis requires close interaction between pharmaceutical companies and regulatory authorities to address topics like relevant (surrogate) endpoints to achieve meaningful readouts faster.
摘要：
■肝纤维化代表了一种未满足的医疗条件，发病率不断上升，治疗选择有限。干扰失调的基因表达被认为是一种特定的治疗方法，我们在这里回顾了当前的选择，以调节转录和翻译与相关酶的小分子抑制剂，转录因子或通过使用非编码RNA分子（RNA干扰）或DNA反义寡核苷酸。尽管在临床前模型中取得了有希望的结果，只有有限的数据可从人类的研究。
■此专家意见提供了有关如何干扰基因表达（转录和翻译）的一般概述，并强调了肝纤维化方面的最新成就。
■开发了许多在肝纤维化(模型)中调节基因表达的化合物作为抗癌剂。它们在肝功能受损的人类中的使用通常由于缺乏特异性以仅抑制肝脏中的纤维化相关基因以及相关的一般毒性和狭窄的治疗窗口而受到损害。RNAi方法显示出更高程度的特异性和潜在更低的全身毒性。肝纤维化的临床发展需要制药公司和监管机构之间的密切互动，以解决相关（替代）终点等主题，以更快地实现有意义的读数。
■此专家意见提供了有关如何干扰基因表达（转录和翻译）的一般概述，并强调了肝纤维化方面的最新成就。
■开发了许多在肝纤维化(模型)中调节基因表达的化合物作为抗癌剂。它们在肝功能受损的人类中的使用通常由于缺乏特异性以仅抑制肝脏中的纤维化相关基因以及相关的一般毒性和狭窄的治疗窗口而受到损害。RNAi方法显示出更高程度的特异性和潜在更低的全身毒性。肝纤维化的临床发展需要制药公司和监管机构之间的密切互动，以解决相关（替代）终点等主题，以更快地实现有意义的读数。
