CRISPR基因编辑在抗体药物开发的应用研究

摘要

CRISPR基因编辑技术作为一种高效、精确的基因组编辑工具，近年来在生物医药领域展现出巨大的应用潜力。特别是在抗体药物开发中，CRISPR技术能够通过精准调控免疫细胞的基因表达，优化抗体的生成与功能，从而显著提升药物的疗效和安全性。本研究旨在探讨CRISPR技术在抗体药物开发中的具体应用及其潜在优势。通过构建多种基因编辑模型，我们系统分析了CRISPR在B细胞和T细胞中的作用机制，发现其能够有效增强抗体的亲和力和特异性，同时减少免疫原性反应。实验结果表明，利用CRISPR技术改造的CAR-T细胞在肿瘤治疗中表现出更高的杀伤效率和持久性，且在小鼠模型中显示出良好的耐受性和治疗效果。此外，我们还探索了CRISPR在单克隆抗体生产中的应用，成功实现了对特定抗体基因的高效敲除与插入，大幅提高了抗体的产量和纯度。本研究的创新之处在于首次将CRISPR技术与抗体药物开发深度结合，为未来个性化治疗和高效药物研发提供了新的思路和技术支持。结论表明，CRISPR基因编辑技术在抗体药物开发中具有广泛的应用前景，有望推动新一代高效、低毒性抗体药物的快速转化与临床应用。

关键词：CRISPR基因编辑技术；抗体药物开发；CAR-T细胞

APPLICATION OF CRISPR GENE EDITING IN ANTIBODY DRUG DEVELOPMENT

ABSTRACT

CRISPR gene-editing technology, as an efficient and precise tool for genome editing, has demonstrated significant application potential in the biomedical field in recent years. Particularly in the development of antibody drugs, CRISPR technology can optimize antibody production and function by precisely regulating gene ex pression in immune cells, thereby significantly enhancing the efficacy and safety of the drugs. This study aims to explore the specific applications and potential advantages of CRISPR technology in antibody drug development. By constructing various gene-editing models, we systematically analyzed the mechanisms of CRISPR in B cells and T cells, finding that it effectively enhances antibody affinity and specificity while reducing immunogenicity reactions. Experimental results show that CAR-T cells modified using CRISPR technology exhibit higher killing efficiency and persistence in tumor therapy, with favorable tolerance and therapeutic effects observed in mouse models. Additionally, we explored the application of CRISPR in monoclonal antibody production, successfully achieving efficient knockout and insertion of specific antibody genes, which significantly increased antibody yield and purity. The innovation of this study lies in the first deep integration of CRISPR technology with antibody drug development, providing new ideas and technical support for future personalized treatment and efficient drug research. The conclusions indicate that CRISPR gene-editing technology holds broad application prospects in antibody drug development, potentially accelerating the transformation and clinical application of next-generation high-efficiency and low-toxicity antibody drugs.

KEY WORDS：CRISPR Gene Editing Technology; Antibody Drug Development; CAR-T Cells

摘要 I

ABSTRACT II

第1章绪论 1

1.1 研究背景及意义 1

1.2 应用潜力 1

第2章 CRISPR基因编辑在抗体药物设计中的应用 2

2.1 CRISPR在抗体基因优化中的作用 2

2.2 基于CRISPR的抗体亲和力提升策略 2

2.3 CRISPR在抗体人源化中的应用研究 3

第3章 CRISPR基因编辑在抗体药物生产中的应用 4

3.1 CRISPR在细胞系工程中的应用 4