Short paper

AAV-mediated gene therapy for metabolic diseases: dosage and reapplication studies in the molybdenum cofactor deficiency model

Rita Hahnewald , Waja Wegner and Jochen Reiss

Institut für Humangenetik der Universität Göttingen, Heinrich-Düker-Weg 12, 37073 Göttingen, Germany

author email corresponding author email

Genetic Vaccines and Therapy 2009, 7:9doi:10.1186/1479-0556-7-9

Published:	18 June 2009

Abstract

In a mouse model for molybdenum cofactor deficiency as an example for an inherited metabolic disease we have determined the dosage of recombinant AAV necessary to rescue the lethal deficiency phenotype. We demonstrated long-term expression of different expression cassettes delivered in a chimeric AAV capsid of serotype 1/2 and compared different routes of application. We then studied the effect of double and triple injections at different time points after birth and found a short neonatal window for non-response of the immune system. Exposition with rAAV capsids within this window allows transgene expression after a second rAAV transduction later. However, exposition within this window does not trigger immunotolerance to the viral capsid, which limits rAAV-mediated refurbishment of the transgene to only one more application outside this permissive window.