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

ChemMedChem

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

Published: May 2021

AI Article Synopsis

  • Enzymatic nanoreactors were developed by encapsulating the enzyme galactose-1-phosphate uridylyl-transferase (GALT) into plant virus capsids using a self-assembly method.
  • The goal was to create virus-like nanoparticles for enzyme-replacement therapy to treat classic galactosemia, with evaluated encapsulation efficiency and catalytic activity showing a 16% activity rate compared to the free enzyme.
  • The nanoreactors demonstrated the ability to be taken up by various cell lines, particularly hepatocytes, highlighting their potential for therapeutic applications in classic galactosemia treatment.

Article 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.

Download full-text PDF

Source
http://dx.doi.org/10.1002/cmdc.202000999DOI Listing

Publication Analysis

Top Keywords

classic galactosemia
12
enzymatic nanoreactors
12
free enzyme
8
galt
5
virus-based nanoreactors
4
nanoreactors galt
4
galt activity
4
activity classic
4
galactosemia therapy
4
therapy enzymatic
4

Similar Publications

Article Synopsis
  • A study called ACTION-Galactosemia Kids evaluated the effects of govorestat, a drug for Classic Galactosemia, on children aged 2-17 by comparing it to a placebo over 18 months.
  • Govorestat showed a significant and lasting reduction in plasma galactitol levels, leading to stabilization or improvement in various clinical measures like behavior and daily living skills, while the placebo group showed decline.
  • Despite its benefits, govorestat did not show improvements in speech or gross motor skills, and both the drug and placebo groups experienced similar rates of adverse effects, indicating it is safe and well tolerated.
View Article and Find Full Text PDF

Monosaccharides improve symptoms of an animal model for type III galactosemia, through the activation of the insulin pathway.

Biomed Pharmacother

December 2024

Centro Andaluz de Biología del Desarrollo (CABD) - Universidad Pablo de Olavide (UPO), Departamento de Biología Molecular e Ingeniería Bioquímica, UPO/CSIC/JA, Sevilla 41013, Spain. Electronic address:

Type III galactosemia is characterized by the inability to metabolize galactose due to deficiency of the UDP-galactose-4-epimerase (GALE) gene, which catalyzes the interconversion of UDP-Galactose and UDP-Glucose. Additionally, GALE interconverts UDP-N-Acetylgalactosamine and UDP-N-Acetylglucosamine. These four sugars are needed for glycosylation of biomolecules.

View Article and Find Full Text PDF
Article Synopsis
  • - Classic galactosemia (CG) is linked to mutations in the GALT gene and leads to early ovarian insufficiency (POI) in 80% of women due to a decrease in ovarian reserve, though the underlying mechanisms are still unclear.
  • - This study utilized advanced techniques like single-nucleus RNA sequencing to analyze ovary biopsies from prepubertal girls with CG, revealing seven key cell types and identifying disruptions in gene expression related to stress responses and cell survival.
  • - The research highlighted significant changes in signaling pathways associated with ovarian function, indicating increased cellular stress and damage in primordial follicles, which could explain accelerated follicular loss in CG patients.
View Article and Find Full Text PDF
Article Synopsis
  • The study presents a rare case of two 9-year-old twins with galactose mutarotase (GALM) deficiency who have remained asymptomatic, even after gradually reintroducing galactose into their diet after a period of strict dietary restriction.
  • Initial detection was through newborn screening, leading to biochemical normalization after dietary adjustments; the genetic analysis revealed a complete deletion of a specific exon in the GALM gene.
  • The findings suggest that dietary liberalization may not negatively affect health in GALM deficiency, prompting further exploration into dietary management for this condition.
View Article and Find Full Text PDF

Background: Classic galactosemia is a rare inherited metabolic disease with long-term complications, particularly in the psychosocial domain. Patients report a lower quality of social life, difficulties in interactions and social relationships, and a lower mental health. We hypothesised that social cognition deficits could partially explain this psychological symptomatology.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!