Nonreplicative genomic HSV-1 derived vectors for dorsal root ganglion gene therapy of Friedreich´s ataxia

María Ventosa Rosales, Directores de la Tesis: Filip Lim (dir. tes.) Lectura: En la Universidad Autónoma de Madrid ( España ) en 2016. Idioma: inglés

Our approach has consisted on the construction and preliminary characterization of a high capacity nonreplicative genomic HSV-1 vector carrying a reduced version of the human FXN genomic locus, comprising the 5 kb promoter and the FXN cDNA with the inclusion of intron 1. We show that the nonreplicative HSV-1 genomic vector deleted for 23 kb maintains its growth capacity and the FXN transgene cassette contains the elements necessary to preserve physiological neuronal regulation of human FXN expression.
Transduction of cultured fetal rat DRG neurons with the 27_4_Or2_β22 FXNinlZ vector results in sustained expression of human FXN transcripts and FXN protein. Rat footpad inoculation with the 27_4_Or2_β22 FXNinlZ vector results in human FXN transgene delivery to the DRG, with expression persisting for at least 1 month.
Our results support the feasibility of using this vector for sustained neuronal expression of human FXN for future FRDA gene therapy.


Nonreplicative genomic HSV-1 derived vectors for dorsal root ganglion gene therapy of Friedreich´s ataxia