RT Journal Article
T1 Delivery of the 135 kb human frataxin genomic DNA locus gives rise to different frataxin isoforms
A1 Pérez Luz, Sara
A1 Gimenez-Cassina, Alfredo
A1 Fernández-Frías, Iván
A1 Wade-Martins, Richard
A1 Díaz-Nido, Javier
AB Friedreich's ataxia (FRDA) is the most common form of hereditary ataxia caused by recessive mutations in the FXN gene. Recent results have indicated the presence of different frataxin isoforms due to alternative gene expression  mechanisms. Our previous studies demonstrated the advantages of using high-capacity herpes simplex virus type 1 (HSV-1) amplicon vectors containing the entire FXN genomic locus (iBAC-FXN) as a gene-delivery vehicle capable of ensuring physiologically-regulated and long-term persistence. Here we describe how expression from the 135 kb human FXN genomic locus produces the three frataxin isoforms both in cultured neuronal cells and also in vivo. Moreover, we also observed the correct expression of these frataxin isoforms in patientderived cells after delivery of the iBAC-FXN. These results lend further support to the potential use of HSV-1 vectors containing entire genomic loci whose expression is mediated by complex transcriptional and posttranscriptional mechanisms for gene therapy applications.
PB Elsevier
YR 2015
FD 2015-05-28
LK https://hdl.handle.net/20.500.14352/102046
UL https://hdl.handle.net/20.500.14352/102046
LA eng
DS Docta Complutense
RD 7 abr 2025