Virus‐Based Nanoreactors with GALT Activity for Classic Galactosemia Therapy

• Published in: ChemMedChem Vol. 16; no. 9; pp. 1438 - 1445
• Main Authors: Gama, Pedro, Cadena‐Nava, Ruben D., Juarez‐Moreno, Karla, Pérez‐Robles, Javier, Vazquez‐Duhalt, Rafael
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 06.05.2021
• Subjects: Animals; bio-nanoreactor; Bromovirus - metabolism; Capsid Proteins - chemistry; Capsid Proteins - isolation & purification; Capsids; Cell Line; Cell lines; classic galactosemia; Coat protein; Drug Compounding - methods; Encapsulation; Endocytosis; Enzymes; Fluorescein-5-isothiocyanate - chemistry; Galactose; galactose-1-phosphate uridylyl-transferase; Galactosemia; Galactosemias - drug therapy; Galactosemias - pathology; GALT; Hepatocytes; Humans; Kinetics; Mice; Nanoparticles; Nanotechnology; Plant viruses; Substrate preferences; Substrates; UTP-Hexose-1-Phosphate Uridylyltransferase - chemistry; UTP-Hexose-1-Phosphate Uridylyltransferase - metabolism; UTP-Hexose-1-Phosphate Uridylyltransferase - therapeutic use; virus-like nanoparticles; Viruses; bio-nanoreactor; GALT; classic galactosemia; galactose-1-phosphate uridylyl-transferase; virus-like nanoparticles
• ISSN: 1860-7179; 1860-7187
• DOI: 10.1002/cmdc.202000999

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. A new Enzyme Replacement Therapy: Innovative enzymatic nanoreactors with GALT activity and without any functionalization have been effectively internalized into different cell lines including fibroblast, kidney cells, and hepatocytes. The encapsulation of GALT in virus‐like nanoparticles could modulate and improve factors such as local enzyme concentration or enzyme stability and give protection against proteases.