摘 要
基因编辑技术，尤其是CRISPR/Cas9系统的发展，为药物研发带来了革命性的变革。传统药物研发面临周期长、成本高及靶点选择性差等问题，而基因编辑技术能够精准定位并修饰特定基因序列，为解决上述问题提供了新思路。本研究旨在探讨基因编辑技术在药物研发中的应用潜力，通过构建多种疾病模型，利用基因编辑技术对关键致病基因进行敲除或修饰，结合高通量筛选平台，评估其对药物敏感性和疗效的影响。研究采用CRISPR/Cas9介导的基因编辑方法，在细胞和动物水平上验证了该技术的有效性，发现经过基因编辑处理后，药物作用机制更加明确，靶向性显著提高，同时降低了脱靶效应。此外，通过对不同编辑策略的优化，成功建立了多个稳定表达的细胞系，为后续药物筛选提供了理想的工具。本研究不仅拓展了基因编辑技术的应用范围，还为个性化医疗提供了理论依据和技术支持，特别是针对遗传性疾病和肿瘤等复杂疾病的治疗方案设计具有重要参考价值。研究表明，基因编辑技术与药物研发的结合将极大提升新药开发效率，缩短研发周期，降低失败风险，有望成为未来药物研发领域的重要发展方向。
关键词：基因编辑技术；CRISPR/Cas9；药物研发；靶向性；脱靶效应
Abstract
The development of gene editing technologies, particularly the CRISPR/Cas9 system, has brought about revolutionary changes in drug discovery. Traditional drug development faces challenges such as long timelines, high costs, and poor target selectivity, whereas gene editing technologies can precisely locate and modify specific gene sequences, offering new approaches to address these issues. This study aims to explore the potential applications of gene editing technologies in drug discovery by constructing multiple disease models and using gene editing techniques to knockout or modify key pathogenic genes. Combined with high-throughput screening platforms, the impact on drug sensitivity and efficacy was evaluated. The research employed CRISPR/Cas9-mediated gene editing methods to validate the effectiveness of this technology at both cellular and animal levels. It was found that after gene editing treatment, drug mechanisms became more clearly defined, target specificity significantly improved, and off-target effects were reduced. Additionally, through optimization of different editing strategies, several stably expressing cell lines were successfully established, providing ideal tools for subsequent drug screening. This study not only expands the application scope of gene editing technologies but also provides theoretical basis and technical support for personalized medicine, especially in designing therapeutic strategies for complex diseases such as genetic disorders and cancer. The findings indicate that the integration of gene editing technologies with drug discovery will greatly enhance the efficiency of new drug development, shorten the R cycle, reduce failure risks, and is expected to become a significant direction in future drug discovery fields.
Keywords：Gene Editing Technology；Crispr/Cas9；Drug Development；Targeting；Off-Target Effects
目 录
摘 要 I
Abstract II
引 言 1
第一章 基因编辑技术概述 2
1.1 基因编辑技术原理 2
1.2 主要基因编辑工具 2
1.3 技术发展历程与现状 3
第二章 疾病模型构建中的应用 5
2.1 构建遗传疾病模型 5
2.2 模型验证与优化 5
2.3 应用于药物筛选平台 6
第三章 药物靶点发现与验证 8
3.1 靶点识别新策略 8
3.2 功能性基因筛选 8
3.3 靶点有效性评估 9
第四章 临床前研究与转化应用 11
4.1 安全性评价体系 11
4.2 个性化医疗探索 11
4.3 产业化前景展望 12
结 论 14
参考文献 15
致 谢 16
