文章：

RNA干扰在临床中的应用：挑战与未来方向

RNA interference in the clinic: challenges and future directions

原文发布日期：2010-12-16

DOI: 10.1038/nrc2966

类型: Review Article

开放获取: 否

要点：

1. Many cancer targets are difficult to block with conventional therapies. Although RNA interference (RNAi) as a therapeutic approach is appealing, many challenges to delivery must be overcome.
2. Nanoparticles hold promise for the safe and effective intracellular delivery of RNAi-based molecules.
3. Physiological barriers and systemic toxicity of nanoparticle-based carrier systems create multiple challenges to bringing RNAi-based therapeutics to the clinic.
4. Nanoparticles can be used to help avoid immune-mediated responses to systemic RNAi-based therapy.
5. Solutions to improving tumour specificity and the ability to monitor and control short-term and long-term RNAi-based therapies are crucial next steps before clinical use.
6. As the technology for delivery improves, so we will also need to improve our understanding of the heterogeneity of RNAi processing in different cancer types.
7. Various resistance mechanisms to RNAi-based therapies must be anticipated.

要点翻译：

1. 许多癌症靶点难以通过常规疗法阻断。尽管RNA干扰疗法作为一种治疗手段颇具吸引力，但其递送过程仍需克服诸多挑战。
2. 纳米颗粒为RNAi分子的安全有效胞内递送带来希望。
3. 基于纳米颗粒的载体系统面临的生理屏障和全身毒性问题，为RNAi疗法进入临床设置了多重障碍。
4. 纳米颗粒有助于避免系统性RNAi疗法引发的免疫介导反应。
5. 在临床应用前，提高肿瘤特异性、提升对短期和长期RNAi疗法的监测与控制能力，是至关重要的下一步。
6. 随着递送技术的进步，我们还需加深对不同癌症类型中RNAi处理异质性的理解。
7. 必须预先考虑针对RNAi疗法的各种耐药机制。

英文摘要：

Inherent difficulties with blocking many desirable targets using conventional approaches have prompted many to consider using RNA interference (RNAi) as a therapeutic approach. Although exploitation of RNAi has immense potential as a cancer therapeutic, many physiological obstacles stand in the way of successful and efficient delivery. This Review explores current challenges to the development of synthetic RNAi-based therapies and considers new approaches to circumvent biological barriers, to avoid intolerable side effects and to achieve controlled and sustained release.

摘要翻译： 

传统方法难以阻断许多理想靶点，这促使人们考虑将RNA干扰（RNAi）作为治疗手段。尽管利用RNAi作为癌症疗法潜力巨大，但生理障碍重重，阻碍了其成功且高效的递送。本文综述了开发合成RNAi疗法所面临的当前挑战，并探讨了绕过生物屏障、避免不可耐受副作用以及实现可控且持续释放的新策略。

原文链接：

RNA interference in the clinic: challenges and future directions