PDF(Pubmed)
Abstract：
Rare diseases (RD) affect a small number of people compared to the general population and are mostly genetic in origin. The first clinical signs often appear at birth or in childhood, and patients endure high levels of pain and progressive loss of autonomy frequently associated with short life expectancy. Until recently, the low prevalence of RD and the gatekeeping delay in their diagnosis have long hampered research. The era of nucleic acid (NA)-based therapies has revolutionized the landscape of RD treatment and new hopes arise with the perspectives of disease-modifying drugs development as some NA-based therapies are now entering the clinical stage. Herein, we review NA-based drugs that were approved and are currently under investigation for the treatment of RD. We also discuss the recent structural improvements of NA-based therapeutics and delivery system, which overcome the main limitations in their market expansion and the current approaches that are developed to address the endosomal escape issue. We finally open the discussion on the ethical and societal issues that raise this new technology in terms of regulatory approval and sustainability of production.
摘要：
与普通人群相比，罕见疾病（RD）影响少数人，并且大多是遗传起源。最初的临床体征通常出现在出生时或儿童时期，患者忍受高水平的疼痛和逐渐丧失自主性，通常与预期寿命短有关。直到最近,RD的低患病率和诊断延迟一直阻碍着研究。基于核酸（NA）的疗法的时代彻底改变了RD治疗的格局，随着一些基于NA的疗法现在进入临床阶段，随着疾病改善药物开发的前景出现了新的希望。在这里，我们回顾了已批准并正在研究治疗RD的基于NA的药物.我们还讨论了基于NA的疗法和递送系统的最新结构改进，它克服了市场扩张中的主要限制，以及为解决内体逃逸问题而开发的当前方法。最后，我们开始讨论在监管批准和生产可持续性方面提出这项新技术的道德和社会问题。
