Journal article
AAV2-mediated gene therapy for Bietti crystalline dystrophy provides functional CYP4V2 in multiple relevant cell models
JH Wang, GE Lidgerwood, M Daniszewski, ML Hu, GE Roberts, RCB Wong, SSC Hung, ME McClements, AW Hewitt, A Pébay, DG Hickey, TL Edwards
Scientific Reports | Published : 2022
Open access
Abstract
Bietti crystalline dystrophy (BCD) is an inherited retinal disease (IRD) caused by mutations in the CYP4V2 gene. It is a relatively common cause of IRD in east Asia. A number of features of this disease make it highly amenable to gene supplementation therapy. This study aims to validate a series of essential precursor in vitro experiments prior to developing a clinical gene therapy for BCD. We demonstrated that HEK293, ARPE19, and patient induced pluripotent stem cell (iPSC)-derived RPE cells transduced with AAV2 vectors encoding codon optimization of CYP4V2 (AAV2.coCYP4V2) resulted in elevated protein expression levels of CYP4V2 compared to those transduced with AAV2 vectors encoding wild t..
View full abstractGrants
Awarded by National Health and Medical Research Council
Funding Acknowledgements
We acknowledge instrument training and support provided by the Biological Optical Microscopy Platform (BOMP), the University of Melbourne. This work was supported by grants from the Ophthalmic Research Institute of Australia, National Stem Cell Foundation of Australia, and Marjorie May Kingston Charitable Trust. T.L.E. was supported by the University of Melbourne Annemarie Mankiewicz-Zelkin Fellowship. D.G.H. was supported by a Hector Maclean Scholarship. G.E.L. is supported by the DHB Foundation and A.P. by a NHMRC Senior Research Fellowship (1153498). The Centre for Eye Research Australia receives Operational Infrastructure Support from the Victorian Government.