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具有半乳糖血症治疗中GALT活性的基于病毒的纳米反应器

Virus-Based Nanoreactors with GALT Activity for Classic Galactosemia Therapy.

作者信息

Gama Pedro, Cadena-Nava Ruben D, Juarez-Moreno Karla, Pérez-Robles Javier, Vazquez-Duhalt Rafael

机构信息

Department of Bionanotechnology, Centro de Nanociencias y Nanotecnología, Universidad Nacional Autónoma de México, Ensenada, Baja California, Mexico.

出版信息

ChemMedChem. 2021 May 6;16(9):1438-1445. doi: 10.1002/cmdc.202000999. Epub 2021 Feb 17.

DOI:10.1002/cmdc.202000999
PMID:33595183
Abstract

Enzymatic nanoreactors were obtained by galactose-1-phosphate uridylyl-transferase (GALT) encapsulation into plant virus capsids by a molecular self-assembly strategy. The aim of this work was to produce virus-like nanoparticles containing GALT for an enzyme-replacement therapy for classic galactosemia. The encapsulation efficiency and the catalytic constants of bio-nanoreactors were determined by using different GALT and virus coat protein ratios. The substrate affinity of nanoreactors was slightly lower than that of the free enzyme; the activity rate was 16 % of the GALT free enzyme. The enzymatic nanoreactors without functionalization were internalized into different cell lines including fibroblast and kidney cells, but especially into hepatocytes. The enzymatic nanoreactors are an innovative enzyme preparation with potential use for the treatment of classic galactosemia.

摘要

通过分子自组装策略将1-磷酸半乳糖尿苷酰转移酶(GALT)封装到植物病毒衣壳中,从而获得酶促纳米反应器。这项工作的目的是制备含有GALT的病毒样纳米颗粒,用于经典半乳糖血症的酶替代疗法。通过使用不同的GALT与病毒衣壳蛋白比例,测定了生物纳米反应器的包封效率和催化常数。纳米反应器的底物亲和力略低于游离酶;活性速率为游离GALT酶的16%。未功能化的酶促纳米反应器可内化到包括成纤维细胞和肾细胞在内的不同细胞系中,尤其是肝细胞。酶促纳米反应器是一种创新的酶制剂,具有治疗经典半乳糖血症的潜在用途。

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