tailieunhanh - Báo cáo sinh học: "AAV-mediated gene therapy for metabolic diseases: dosage and reapplication studies in the molybdenum cofactor deficiency model"

Tuyển tập các báo cáo nghiên cứu về sinh học được đăng trên tạp chí sinh học Journal of Biology đề tài: AAV-mediated gene therapy for metabolic diseases: dosage and reapplication studies in the molybdenum cofactor deficiency model | Genetic Vaccines and Therapy BioMed Central 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 Open Access Address Institut fur Humangenetik der Universitat Gottingen Heinrich-Duker-Weg 12 37073 Gottingen Germany Email Rita Hahnewald - Waja Wegner - Jochen Reiss - jreiss@ Corresponding author Published 18 June 2009 Received 20 March 2009 Genetic Vaccines and Therapy 2009 7 9 doi 186 1479-0556-7-9 Accepted 18 June 2009 This article is available from http content 7 1 9 2009 Hahnewald et al licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License http licenses by which permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited. 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. Findings In mammals molybdenum cofactor MoCo is essential for the activity of sulfite oxidase xanthine dehydrogenase and aldehyde oxidase 1