Hosseinidoust Zeinab
Department of Chemical Engineering, Faculty of Engineering, McMaster University, Hamilton, Ontario. Canada.
Curr Gene Ther. 2017;17(2):120-126. doi: 10.2174/1566523217666170510151940.
Bacteriophages (bacterial viruses) have long been under investigation as vectors for gene therapy. Similar to other viral vectors, the phage coat proteins have evolved over millions of years to protect the viral genome from degradation post injection, offering protection for the valuable therapeutic sequence.
However, what sets phage apart from other viral gene delivery vectors is their safety for human use and the relative ease by which foreign molecules can be expressed on the phage outer surface, enabling highly targeted gene delivery. The latter property also makes phage a popular choice for gene therapy target discovery through directed evolution. Although promising, phage-mediated gene therapy faces several outstanding challenges, the most notable being lower gene delivery efficiency compared to animal viruses, vector stability, and nondesirable immune stimulation.
This review presents a critical review of promises and challenges of employing phage as gene delivery vehicles as well as an introduction to the concept of phage-based microbiome therapy as the new frontier and perhaps the most promising application of phage-based gene therapy.
长期以来，噬菌体（细菌病毒）一直被作为基因治疗的载体进行研究。与其他病毒载体类似，噬菌体外壳蛋白经过数百万年的进化，可保护病毒基因组在注射后不被降解，从而为有价值的治疗序列提供保护。
然而，噬菌体与其他病毒基因递送载体的不同之处在于其对人类使用的安全性，以及能相对容易地在噬菌体外表面表达外源分子，从而实现高度靶向的基因递送。后一特性也使噬菌体成为通过定向进化发现基因治疗靶点的热门选择。尽管前景广阔，但噬菌体介导的基因治疗面临若干突出挑战，最显著的是与动物病毒相比基因递送效率较低、载体稳定性以及不良免疫刺激。
本综述对将噬菌体用作基因递送载体的前景与挑战进行了批判性审视，并介绍了基于噬菌体的微生物组治疗概念，这是基于噬菌体的基因治疗的新前沿，或许也是最有前景的应用。
