Loessner Holger, Weiss Siegfried
Molecular Immunology, GBF, German Research Centre for Biotechnology, Mascheroder Weg 1, D-38124 Braunschweig, Germany.
Expert Opin Biol Ther. 2004 Feb;4(2):157-68. doi: 10.1517/14712598.4.2.157.
The use of live attenuated bacterial vaccine strains allows the targeted delivery of macromolecules to mammalian cells and tissues via the mucosal route. Depending on their specific virulence mechanisms and inherent metabolic preferences, bacteria invade certain cell types and body niches where they consequently deliver their cargo. Recently, the ability of attenuated strains of Salmonella, Shigella and Yersinia spp., as well as Listeria monocytogenes and invasive Escherichia coli, to deliver eukaryotic expression plasmids into mammalian cells in vitro and in vivo has been discovered. The great potential of bacteria-mediated transfer of plasmid DNA encoding vaccine antigens and/or therapeutic molecules was demonstrated in experimental animal models of infectious diseases, tumours and gene deficiencies. The exact mechanism of DNA transfer from the bacterial vector into the mammalian host is not yet completely known. The understanding of molecular events during bacterial DNA transfer, however, will further the development of bacterial vector systems with great promise for various clinical applications.
使用减毒活细菌疫苗菌株可通过黏膜途径将大分子靶向递送至哺乳动物细胞和组织。根据其特定的毒力机制和固有的代谢偏好，细菌会侵入某些细胞类型和身体微环境，并在其中递送其携带的物质。最近，已发现沙门氏菌、志贺氏菌和耶尔森氏菌属的减毒株，以及单核细胞增生李斯特菌和侵袭性大肠杆菌在体外和体内将真核表达质粒递送至哺乳动物细胞的能力。在传染病、肿瘤和基因缺陷的实验动物模型中，证明了细菌介导的编码疫苗抗原和/或治疗分子的质粒DNA转移具有巨大潜力。细菌载体中的DNA转移至哺乳动物宿主的确切机制尚未完全明确。然而，对细菌DNA转移过程中分子事件的了解将推动具有广阔临床应用前景的细菌载体系统的发展。
