7. Conclusions 7.结论
While PT has recently received greatly increased attention and its prospects appear promising, the potential application of that therapy in treating diseases of the nervous system has rarely been mentioned. Nevertheless, there are some data in the literature and preliminary studies that strongly suggest that the CNS and peripheral nervous system could indeed be targeted by that therapy. Thus, PT could be used as a weapon against bacterial infections of the CNS. Furthermore, recently described immunomodulating and anti-inflammatory effects of phages could pave the way towards their use in treating autoimmune diseases of the nervous system. In addition, phage engineering could allow the use of such modified phages in the fight against some neoplasms of the CNS. It is therefore likely that classical PT as well as “repurposed” PT could provide more efficient means of treatment of both bacterial and non-bacterial diseases of the nervous system.
近来，PT 疗法受到越来越多的关注，其前景似乎也很广阔，但该疗法在治疗神经系统疾病方面的潜在应用却很少被提及。然而，一些文献和初步研究数据有力地表明，中枢神经系统和外周神经系统确实可以成为该疗法的目标。因此，PT 可以作为对抗中枢神经系统细菌感染的武器。此外，最近描述的噬菌体的免疫调节和抗炎作用可以为它们用于治疗神经系统的自身免疫性疾病铺平道路。此外，噬菌体工程学还可以将这种改良噬菌体用于抗击中枢神经系统的某些肿瘤。因此，传统的噬菌体疗法和 “再利用 “的噬菌体疗法有可能为治疗神经系统的细菌性和非细菌性疾病提供更有效的方法。
8. Future Perspective 8.未来展望
The current state of the research in the treatment of bacterial infections in the CNS indicates that this area is vastly unexplored. While some foundational research has been conducted, there is much potential for broadening the search for phages specific to bacterial strains that commonly infect the CNS. Although partial ground research has been carried out, it will be highly beneficial if a wide search for phages specific to bacteria commonly infecting the CNS is initiated. After that, the next crucial step would be to determine phage pharmacokinetics, host range, stability, and safety. Then, universal and easily monitored models should be created to study penetration through the BBB of natural and modified bacteriophages, as well as phage-based nanocarriers and their effectiveness in delivering drugs to the targeted tissues and cells. One more highly important direction is testing larger groups of subjects with the treatment regimens that show promising results. One future possibility is bacteriophage-based modifications of the composition of gut microbiota to improve the efficiency of cognitive processes Another field altogether is cancer research, where bacteriophages might fit perfectly due to their natural properties and opportunities provided by the phage display technique—yet their potential is still underexploited. The only issue is if the phage constructs would effectively penetrate the BBB and how—if at all—the immune system would be activated by these particles. Excitingly, recent publications in 2022 have linked bacteriophages with CRISPR-like antiviral systems, a groundbreaking development [241,242,243,244,245,246]. Bacteriophage antiviral systems belong to all six known types of CRISPR-Cas systems and occur as divergent and hypercompact antiviral systems. Some of these systems lack key components, which suggests alternative functional roles or host complementation [246]. There are even reports of using the CRISPR-Cas system to genetically modify bacteriophages, thus giving them new mechanisms of action [247], which is an interesting perspective in the context of therapeutic phage applications.
治疗中枢神经系统细菌感染的研究现状表明，这一领域尚未得到广泛开发。虽然已经开展了一些基础性研究，但扩大寻找中枢神经系统常见感染细菌菌株特异性噬菌体的工作仍大有可为。虽然已经开展了部分基础研究，但如果能开始广泛寻找中枢神经系统常见感染细菌的特异性噬菌体，将大有裨益。之后，下一个关键步骤将是确定噬菌体的药代动力学、宿主范围、稳定性和安全性。然后，应创建通用且易于监测的模型，以研究天然和改良噬菌体以及基于噬菌体的纳米载体通过 BBB 的穿透性及其向目标组织和细胞递送药物的有效性。还有一个非常重要的方向，就是用显示出良好效果的治疗方案对更大的受试者群体进行测试。另一个领域是癌症研究，由于噬菌体的天然特性和噬菌体展示技术提供的机会，噬菌体可能非常适合癌症研究。唯一的问题是，噬菌体构建体能否有效穿透生物BB，以及这些粒子如何激活免疫系统。令人兴奋的是，最近在 2022 年发表的文章将噬菌体与类似 CRISPR 的抗病毒系统联系在一起，这是一个突破性的进展[ 241, 242, 243, 244, 245, 246]。噬菌体抗病毒系统属于所有六种已知类型的 CRISPR-Cas 系统，并作为分化和超紧凑的抗病毒系统出现。其中一些系统缺乏关键成分，这表明它们具有其他功能作用或宿主互补性[246]。甚至有报道称，利用 CRISPR-Cas 系统对噬菌体进行基因改造，从而赋予它们新的作用机制[247]，这在治疗性噬菌体应用方面是一个有趣的视角。