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用于开发下一代重组疫苗的CRISPR/Cas系统:现状与未来前景

CRISPR/Cas System Toward the Development of Next-Generation Recombinant Vaccines: Current Scenario and Future Prospects.

作者信息

Naeem Muhammad, Alkhodairy Hanoof Fahd, Ashraf Iqra, Khalil Amjad Bajes

机构信息

Department of Bioengineering, King Fahd University of Petroleum and Minerals (KFUPM), Dhahran, 31261 Saudi Arabia.

Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan.

出版信息

Arab J Sci Eng. 2023;48(1):1-11. doi: 10.1007/s13369-022-07266-7. Epub 2022 Sep 23.

Abstract

The initially developed vaccines were relying mostly on attenuation and inactivation of pathogens. The use of recombinant DNA technology allows the targeting of immune responses focused against a few protective antigens. The conventional recombination methods for generating vaccines are time-consuming, laborious, and less efficient. To overcome these limitations, a new precise CRISPR/Cas9 with high efficacy, specificity, and low-cost properties has solved a lot of current problems of recombinant vaccines that intrigued the inspiration for novel recombinant vaccine development. CRISPR/Cas9 system was discovered as a bacterial adaptive immune system. In the domain of virology, CRISPR/Cas9 is used to engineer the virus genome to understand the fundamentals of viral pathogenesis, gene therapy, and virus-host interactions. One step ahead CRISPR/Cass9 bypassed the vaccine to precisely engineer the B-cells to secrete the specific antibodies against deadly viral pathogens. There is a critical literature review gap especially in the use of CRISPR/Cas9 to generate recombinant vaccines against viral diseases and its prospective application to engineering the B-cells in immunocompromised people. This review heights the application of CRISPR/Cas9 compared to conventional approaches for the development of recombinant vaccine vectors, editing the genes of B-cells, and challenges that need to be overcome. The factors affecting CRISPR/Cas9-edited recombinant vaccines and prospects in the context of viral genome editing for the development of vaccines will be discussed.

摘要

最初研发的疫苗主要依赖病原体的减毒和灭活。重组DNA技术的应用使得针对少数保护性抗原的免疫反应成为可能。传统的疫苗重组方法耗时、费力且效率较低。为克服这些局限性,一种新型的具有高效、特异性和低成本特性的精确CRISPR/Cas9技术解决了许多当前重组疫苗所面临的问题,为新型重组疫苗的研发带来了灵感。CRISPR/Cas9系统最初是作为一种细菌适应性免疫系统被发现的。在病毒学领域,CRISPR/Cas9被用于改造病毒基因组,以了解病毒发病机制、基因治疗以及病毒与宿主相互作用的基本原理。更进一步,CRISPR/Cass9绕过了疫苗,直接精确改造B细胞,使其分泌针对致命病毒病原体的特异性抗体。目前存在一个关键的文献综述空白,尤其是在利用CRISPR/Cas9研发针对病毒性疾病的重组疫苗以及将其应用于免疫功能低下人群的B细胞改造方面。本综述着重介绍了与传统方法相比,CRISPR/Cas9在重组疫苗载体开发、B细胞基因编辑以及需要克服的挑战等方面的应用。同时,还将讨论影响CRISPR/Cas9编辑的重组疫苗的因素以及在疫苗开发的病毒基因组编辑背景下的前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4737/9510529/d01d096fd6d9/13369_2022_7266_Fig1_HTML.jpg

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