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蛋白质工程在心血管治疗学中的应用:心脏修复的未开发潜力。

Protein engineering for cardiovascular therapeutics: untapped potential for cardiac repair.

机构信息

From the Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.

出版信息

Circ Res. 2013 Sep 13;113(7):933-43. doi: 10.1161/CIRCRESAHA.113.300215.

Abstract

A number of new and innovative approaches for repairing damaged myocardium are currently undergoing investigation, with several encouraging results. In addition to the progression of stem cell-based approaches and gene therapy/silencing methods, evidence continues to emerge that protein therapeutics may be used to directly promote cardiac repair and even regeneration. However, proteins are often limited in their therapeutic potential by short local half-lives and insufficient bioavailability and bioactivity, and many academic laboratories studying cardiovascular diseases are more comfortable with molecular and cellular biology than with protein biochemistry. Protein engineering has been used broadly to overcome weaknesses traditionally associated with protein therapeutics and has the potential to specifically enhance the efficacy of molecules for cardiac repair. However, protein engineering as a strategy has not yet been used in the development of cardiovascular therapeutics to the degree that it has been used in other fields. In this review, we discuss the role of engineered proteins in cardiovascular therapies to date. Further, we address the promise of applying emerging protein engineering technologies to cardiovascular medicine and the barriers that must be overcome to enable the ultimate success of this approach.

摘要

目前,有许多新的创新方法正在被研究用于修复受损的心肌,其中一些已经取得了令人鼓舞的结果。除了基于干细胞的方法和基因治疗/沉默方法的进展外,越来越多的证据表明,蛋白质治疗剂可直接用于促进心脏修复甚至再生。然而,由于蛋白质的局部半衰期短、生物利用度和生物活性不足,其治疗潜力通常受到限制,许多研究心血管疾病的学术实验室在分子和细胞生物学方面比蛋白质生物化学更得心应手。蛋白质工程已被广泛用于克服与蛋白质治疗剂相关的弱点,并且有可能特异性地提高用于心脏修复的分子的疗效。然而,与其他领域相比,蛋白质工程作为一种策略,尚未在心血管治疗药物的开发中得到广泛应用。在这篇综述中,我们讨论了工程蛋白在心血管治疗中的作用。此外,我们还探讨了将新兴的蛋白质工程技术应用于心血管医学的前景,以及克服这些障碍以实现这种方法的最终成功的必要性。

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