Leuzzi Vincenzo, Rossi Luigia, Gabucci Claudia, Nardecchia Francesca, Magnani Mauro
Department of Child and Adolescent Neuropsychiatry, SAPIENZA University of Rome, Via deiSabelli 108, 00185, Rome, Italy.
Department of Biomolecular Science, University of Urbino, Via Saffi 2, 61029, Urbino, PU, Italy.
J Inherit Metab Dis. 2016 Jul;39(4):519-30. doi: 10.1007/s10545-016-9926-0. Epub 2016 Mar 30.
The possibility to clone, express and purify recombinant enzymes have originated the opportunity to dispose of a virtually infinite array of proteins that could be used in the clinics to treat several inherited and acquired pathological conditions. However, the direct administration of these recombinant proteins faces some intrinsic difficulties, such as degradation by circulating proteases and/or inactivation by the patient immune system. The use of drug delivery systems may overcome these limitations. Concerning recombinant enzyme therapy, the present review will mainly focus on the exploitation of erythrocytes as a carrier system for enzymes removing potentially noxious metabolites from the circulation, either as limiting treatment strategy for auxotrophic tumours or as a detoxing approach for some intoxication type inherited metabolic disorders. Moreover, the possibility of using RBCs as a potential delivering system addressing the enzymes to the monocyte-macrophages of reticular endothelial system for the treatment of diseases associated with this cell lineage, e.g. lysosome storage diseases, will be briefly discussed.
克隆、表达和纯化重组酶的可能性带来了一个机会,即可以获得几乎无穷无尽的蛋白质阵列,这些蛋白质可用于临床治疗多种遗传性和后天性病理状况。然而,直接施用这些重组蛋白面临一些内在困难,例如被循环蛋白酶降解和/或被患者免疫系统灭活。使用药物递送系统可能会克服这些限制。关于重组酶疗法,本综述将主要关注利用红细胞作为酶的载体系统,从循环中去除潜在有害代谢物,这既可以作为营养缺陷型肿瘤的有限治疗策略,也可以作为某些中毒型遗传性代谢紊乱的解毒方法。此外,还将简要讨论使用红细胞作为潜在递送系统,将酶递送至网状内皮系统的单核巨噬细胞以治疗与此细胞谱系相关疾病(如溶酶体贮积病)的可能性。