从技术到治疗的飞跃--基因工程正在为更有效的噬菌体疗法铺平道路。

IF 3.8 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochemical Society transactions Pub Date : 2024-06-26 DOI:10.1042/BST20231289
Jessica M Lewis, Joshua Williams, Antonia P Sagona
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引用次数: 0

摘要

噬菌体(噬菌体)是针对细菌的特异性病毒,能高效、特异地攻击细菌。早在二十世纪初,人们就开始研究噬菌体的抗菌潜力;然而,随着抗生素的普及,噬菌体的应用在很大程度上黯然失色。随着全球抗生素耐药菌株的激增,利用噬菌体进行治疗的热潮再次兴起。噬菌体的主要优势之一是易于改造,可以根据改造情况生成许多具有特定功能的优化衍生物。这些增强型衍生物可以显示出更高的感染性、更广的宿主范围或对人体组织更强的亲和力,而某些细菌物种正是在人体组织中发挥致病作用的。尽管如此,体外衍生物的产生与体内的临床应用之间仍存在明显差异。在大多数情况下,噬菌体疗法只是在所有其他治疗方法都已用尽的情况下,出于同情才使用。缺乏临床试验和众多监管障碍阻碍了噬菌体疗法的发展,进而阻碍了工程变体在临床上的广泛应用。在这篇综述中,我们概述了噬菌体的各种修饰类型,以及这些修饰如何使噬菌体的杀菌功能比野生型噬菌体更强。我们还讨论了转基因噬菌体在临床试验中取得的新进展,以及目前面临的问题,以便将其作为一种疗法应用于临床。
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Making the leap from technique to treatment - genetic engineering is paving the way for more efficient phage therapy.

Bacteriophages (phages) are viruses specific to bacteria that target them with great efficiency and specificity. Phages were first studied for their antibacterial potential in the early twentieth century; however, their use was largely eclipsed by the popularity of antibiotics. Given the surge of antimicrobial-resistant strains worldwide, there has been a renaissance in harnessing phages as therapeutics once more. One of the key advantages of phages is their amenability to modification, allowing the generation of numerous derivatives optimised for specific functions depending on the modification. These enhanced derivatives could display higher infectivity, expanded host range or greater affinity to human tissues, where some bacterial species exert their pathogenesis. Despite this, there has been a noticeable discrepancy between the generation of derivatives in vitro and their clinical application in vivo. In most instances, phage therapy is only used on a compassionate-use basis, where all other treatment options have been exhausted. A lack of clinical trials and numerous regulatory hurdles hamper the progress of phage therapy and in turn, the engineered variants, in becoming widely used in the clinic. In this review, we outline the various types of modifications enacted upon phages and how these modifications contribute to their enhanced bactericidal function compared with wild-type phages. We also discuss the nascent progress of genetically modified phages in clinical trials along with the current issues these are confronted with, to validate it as a therapy in the clinic.

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来源期刊
Biochemical Society transactions
Biochemical Society transactions 生物-生化与分子生物学
CiteScore
7.80
自引率
0.00%
发文量
351
审稿时长
3-6 weeks
期刊介绍: Biochemical Society Transactions is the reviews journal of the Biochemical Society. Publishing concise reviews written by experts in the field, providing a timely snapshot of the latest developments across all areas of the molecular and cellular biosciences. Elevating our authors’ ideas and expertise, each review includes a perspectives section where authors offer comment on the latest advances, a glimpse of future challenges and highlighting the importance of associated research areas in far broader contexts.
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