PuSH - Publikationsserver des Helmholtz Zentrums München: Therapeutic AASS inhibition by AAV-miRNA rescues glutaric aciduria type I severe phenotype in mice.

Informationen

Hinweise zu Qualitätskriterien von Zeitschriften

Open-Access-Richtlinie der Helmholtz-Gemeinschaft 2016

CC Licencences

Metriken für Publikationen

Navigation

Startseite

English

Recherche

Erweiterte Suche

Durchblättern nach ...

... HMGU-Autoren/Konsortien

... Organisationsstruktur

... Zeitschriften

... Publikationstypen

... Forschungsdaten

... Arbeitsgruppen

... Erscheinungsjahr

Publikationen im Überblick

Statistik

HGF Fortschrittsbericht

OA Publikationen

Eintragen

Neue Publikation eintragen

Neue Publikation holen aus...

...EVA

Fehlende Publikation melden

Highlights

Suche

Hilfe & Kontakt

Ansprechpartner

Hilfe

Datenschutz

Helmholtz Open Science

Bibliometrische Indikatoren

SHERPA/RoMEO

DOAJ

Export:

Text

Endnote (RIS) BIB

BibTeX

Segur-Bailach, E.* ; Mateu-Bosch, A.* ; Bofill-De Ros, X.* ; Parés, M.* ; da Silva Buttkus, P. ; Rathkolb, B. ; Gailus-Durner, V. ; Hrabě de Angelis, M. ; Moeini, P.* ; Gonzalez-Aseguinolaza, G.* ; Tort, F.* ; Ribes, A.* ; van Karnebeek, C.D.M.* ; García-Villoria, J.* ; Fillat, C.*

Therapeutic AASS inhibition by AAV-miRNA rescues glutaric aciduria type I severe phenotype in mice.

Mol. Ther. 33, 4820-4833 (2025)

Postprint

DOI

PMC

	Open Access Hybrid

Abstract
Metriken
Zusatzinfos

Glutaric aciduria type I (GA1) is an inherited disorder caused by the enzymatic defect of glutaryl-CoA dehydrogenase in the lysine degradation pathway, characterized by the accumulation of toxic metabolites in the central nervous system. We reasoned that substrate reduction therapy targeting the alpha-Aminoadipic Semialdehyde Synthase (AASS), the first enzyme in the catabolism of lysine, could provide an attractive therapeutic alternative. We explored to reduce the expression of AASS by an artificial microRNA with AASS target sequences embedded in a miR-16 backbone (miR_AASS). We analyzed several delivery routes and AAV serotypes and evaluated the therapeutic efficacy of a systemic neonatal delivery of AAV9_miR_AASS in the Gcdh-/- mouse model of GA1. We detected dose-dependent miR-AASS expression and AASS inhibition in liver and striatum, the main tissues affected in GA1. Treatment with AAV9_miR_AASS in lysine overload challenged mice reduced the accumulation of neurotoxic metabolites, up to six months post-treatment in the striatum, prevented the neuropathological alterations and improved mouse survival. Our results show that AAV9_miR_AASS supports AASS-lowering as a potential gene therapy strategy for GA1.

Impact Factor

Scopus SNIP

Altmetric

0.000