利用微纳技术的生物工程杆状病毒作为新型治疗制剂：原理、前景和挑战。

Bioengineered baculoviruses as new class of therapeutics using micro and nanotechnologies: principles, prospects and challenges.

机构信息

Biomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering and Artificial Cells and Organs Research Centre, Faculty of Medicine, McGill University, 3775 University Street, Montreal, Québec H3A 2B4, Canada; Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Center for Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139, USA.

Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Center for Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139, USA.

出版信息

Adv Drug Deliv Rev. 2014 May;71:115-30. doi: 10.1016/j.addr.2014.01.004. Epub 2014 Feb 3.

DOI:10.1016/j.addr.2014.01.004

PMID:24503281

Abstract

Designing a safe and efficient gene delivery system is required for success of gene therapy trials. Although a wide variety of viral, non-viral and polymeric nanoparticle based careers have been widely studied, the current gene delivery vehicles are limited by their suboptimal, non-specific therapeutic efficacy and acute immunological reactions, leading to unwanted side effects. Recently, there has been a growing interest in insect-cell-originated baculoviruses as gene delivery vehicles for diverse biomedical applications. Specifically, the emergence of diverse types of surface functionalized and bioengineered baculoviruses is posed to edge over currently available gene delivery vehicles. This is primarily because baculoviruses are comparatively non-pathogenic and non-toxic as they cannot replicate in mammalian cells and do not invoke any cytopathic effect. Moreover, emerging advanced studies in this direction have demonstrated that hybridizing the baculovirus surface with different kinds of bioactive therapeutic molecules, cell-specific targeting moieties, protective polymeric grafts and nanomaterials can significantly improve the preclinical efficacy of baculoviruses. This review presents a comprehensive overview of the recent advancements in the field of bioengineering and biotherapeutics to engineer baculovirus hybrids for tailored gene therapy, and articulates in detail the potential and challenges of these strategies for clinical realization. In addition, the article illustrates the rapid evolvement of microfluidic devices as a high throughput platform for optimizing baculovirus production and treatment conditions.

摘要

设计安全有效的基因传递系统是基因治疗试验成功的关键。尽管已广泛研究了多种病毒、非病毒和聚合物纳米颗粒载体，但当前的基因传递载体受到其非最佳、非特异性治疗效果和急性免疫反应的限制，导致不必要的副作用。最近，人们对昆虫细胞起源的杆状病毒作为基因传递载体产生了越来越大的兴趣，用于各种生物医学应用。具体来说，不同类型的表面功能化和生物工程化杆状病毒的出现有望超越目前可用的基因传递载体。这主要是因为杆状病毒在哺乳动物细胞中不能复制，不会引起任何细胞病变效应，因此相对来说没有致病性和毒性。此外，这一领域的新兴高级研究表明，通过将杆状病毒表面与不同种类的生物活性治疗分子、细胞特异性靶向部分、保护性聚合接枝和纳米材料杂交，可以显著提高杆状病毒的临床前疗效。本文全面概述了生物工程和生物治疗领域的最新进展，介绍了用于定制基因治疗的杆状病毒杂交体的工程设计，并详细阐述了这些策略在临床实现方面的潜力和挑战。此外，本文还说明了微流控设备作为优化杆状病毒生产和处理条件的高通量平台的快速发展。