单纯疱疹病毒基因治疗载体的研制

Yoshitaka Miyagawa
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摘要

近年来,基因和细胞疗法作为一种新的治疗方式已被广泛接受,一些基因治疗药物已被批准。这一进步的基础是基因传递工具的创新,特别是病毒载体,它不再仅仅是基础研究中的基因转移工具。基因疗法自问世以来,包括安全性、功能性和生产技术在内的所有方面都得到了显著改善。另一方面,随着基因治疗的临床应用,出现了新的安全性和有效性问题,基因治疗正在进入一个新的阶段。临床前和临床数据都表明,通过基因传递载体的转导,治疗性基因在疾病部位的简单过表达不足以确保安全性和治疗效果。这一领域的成熟将需要更复杂的基因传递载体系统和高度调控的治疗性基因表达系统,以精确地将这些基因引入靶细胞并在适当的时间表达到适当的程度。基于单纯疱疹病毒(HSV)的载体是一种非常安全且功能强大的载体系统,具有应对当前基因和细胞治疗挑战的潜力。这使得HSV载体有望成为基因治疗的基因传递载体。本章将重点介绍HSV作为基因治疗传递载体的当前发展趋势。
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Development of Herpes Simplex Virus-based Vectors for Gene Therapy
In recent years, gene and cell therapies have become widely accepted as new therapeutic modalities, and a number of gene therapy drugs have been approved. Underlying this advance are innovations in gene delivery tools, especially viral vectors, which are no longer simply gene transfer tools in basic research. Since its initial inception, all aspects of gene therapy have been dramatically improved, including their safety, functionality, and production technology. On the other hand, with use of gene therapies clinically, new safety and efficacy concerns have emerged, and gene therapy is now entering a new phase. Both preclinical and clinical data have demonstrated that simple overexpression of a therapeutic gene at a disease site through transduction by a gene delivery vector is not sufficient to ensure safety and therapeutic efficacy. Maturation of this field will require more sophisticated gene delivery vector systems and highly regulated therapeutic gene expression systems to precisely introduce these genes into target cells and express them to the appropriate degree at the appropriate time. Herpes simplex virus (HSV)-based vectors are extremely safe and functional vector systems that have the potential to meet current challenges in gene and cell therapy. This makes HSV vectors promising gene delivery vehicles for gene therapy. This chapter will focus on the current trends in the development of HSV as a delivery vector for gene therapy.
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Journal of Tokyo Medical University
Journal of Tokyo Medical University Medicine-Medicine (all)
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