噬菌体展示技术筛选细胞穿透肽的研究进展

doi:10.11843/j.issn.0366-6964.2025.08.010

摘要/Abstract

摘要：

细胞穿透肽(CPP)是一类由5~30个天然或人造氨基酸残基组成的短肽序列，具有增强细胞摄取抗原并促进穿越各种生物屏障的能力，因其高效、独特的跨膜运输能力成为近年来生物医药领域的研究热点。噬菌体展示技术(PDT)是一种通过对噬菌体DNA进行基因改造，从而在噬菌体表面展示的分子技术，其包含的遗传序列可将表型与基因型相连，该技术允许不同的肽库在噬菌体颗粒表面表达，并能选择与靶标特异性结合的多肽，且其具有简单、高效和低成本等优点。因此，可利用其在不损伤其他正常细胞的情况下实现靶向治疗，为研发靶向递药新型载体，实现靶向药物投递奠定了基础。本文综述了细胞穿透肽以及利用噬菌体展示技术筛选细胞穿透肽的研究进展，同时也为饲用抗生素替代品的研究与开发提供更有效的思路和方法，并进一步为胞内致病菌的精准杀伤提供新的策略和研究方向。

关键词: 细胞穿透肽, 噬菌体展示技术, 靶向, 抗菌肽

Abstract:

Cell penetrating peptide (CPP) is a kind of short peptide sequence consisting of 5~30 natural or artificial amino acid residues, which has the ability to enhance cell uptake of antigens and promote crossing various biological barriers. Because of its efficient and unique transmembrane transport ability, CPP has become a research hotspot in the biomedical field in recent years. Phage display technology (PDT) is a molecular technology to display on the surface of phage by genetic modification of phage DNA, which contains genetic sequences that can connect phenotypes with genotypes. This technology allows different peptide libraries to be expressed on the surface of phage particles, and can select peptides that specifically bind to targets, and it has the advantages of simplicity, high efficiency and low cost.Therefore, it can be used to realize targeted therapy without damaging other normal cells, which lays a foundation for developing new carriers for targeted drug delivery and realizing targeted drug delivery. In this paper, the research progress of cell penetrating peptides and screening cell penetrating peptides by phage display technology is reviewed, which also provides more effective ideas and methods for the research and development of feed antibiotic substitutes, and further provides new strategies and research directions for the precise killing of intracellular pathogens.

Key words: cell-penetrating peptides, phage display technology, targeting, antimicrobial peptide

中图分类号:

田宛鑫, 刘思佳, 姜宁, 赵芳芳, 宋军, 张爱忠. 噬菌体展示技术筛选细胞穿透肽的研究进展[J]. 畜牧兽医学报, 2025, 56(8): 3658-3665.

TIAN Wanxin, LIU Sijia, JIANG Ning, ZHAO Fangfang, SONG Jun, ZHANG Aizhong. Research Progress in Screening Cell Penetrating Peptides by Phage Display Technology[J]. Acta Veterinaria et Zootechnica Sinica, 2025, 56(8): 3658-3665.

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应用 Application	方法 Method	作用效果 Effect	参考文献 References
药物递送 Drug delivery	将CPPs自身或与肿瘤靶向肽(TTP)共同结合到抗癌药物上	可精准递送至肿瘤细胞，提高治疗效果，减少对正常细胞的损伤	[13]
疫苗开发 Vaccine development	利用CPPs将抗原蛋白或核酸等生物活性物质导入抗原呈递细胞	可增强免疫反应，用于疫苗的开发和免疫治疗	[14]
基因治疗 Gene therapy	利用CPPs将基因、小干扰RNA等导入靶细胞	可实现基因的修饰和表达调控，用于治疗相关疾病	[15]
穿越生物屏障 Cross the biological barrier	利用CPPs能够将药物或基因递送到神经细胞	CPPs能够穿越血脑屏障、眼屏障等难以逾越的生物屏障，用于治疗创伤性脑损伤等中枢神经系统疾病	[16]
蛋白质替代疗法 Protein replacement therapy	利用CPPs将功能性蛋白质如酶、抗体、修饰蛋白等引入细胞内	可应用于蛋白质替代疗法、信号通路研究等领域	[17]
生物传感器开发 Biosensor development	利用CPPs共轭SERS纳米传感器，用于细胞周期内单个活细胞的原位细胞内pH成像	可增强纳米传感器的吸收，开发新型的生物传感器和成像探针	[18]

研究领域 Research field	实际应用 Practical application	参考文献 References
抗体药物开发 Antibody drug development	Xu等^[29]识别出一种针对产气荚膜梭菌感染的特异性靶向抗菌肽; Bussel等^[30]开发了一种可以用来治疗免疫性血小板减少性紫癜的促血栓形成蛋白	[29-30]
疫苗开发 Vaccine development	筛选与病毒表面蛋白高度特异的肽或抗体，为开发新的抗病毒药物和疫苗提供重要的候选分子	[31-34]
抗癌研究 Anticancer research	筛选癌特异性抗原肽或抗体并与癌细胞表面特异性标志物结合，实现靶向治疗，减少对正常细胞的损害	[35-36]
生物传感器设计 Design of biosensor	筛选高灵敏度和特异性的传感器，应用于环境监测、食品安全和临床诊断等领域	[37-39]
纳米技术领域 Field of nanotechnology	宋雯妍等^[40]首次筛选出了猪繁殖与呼吸综合征病毒GP5蛋白的特异性纳米抗体; 马继福等^[41]筛选出针对绵羊抑制素α亚基的特异性纳米抗体	[40-41]
靶向基因或药物递送 Targeted gene or drug delivery	筛选出能够特异性识别靶细胞或组织的肽或抗体，将基因或药物精准递送至目标部位，提高治疗效果并减少副作用	[42-44]

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