In vivo targeting of a variant causing vanishing white matter using CRISPR/Cas9

Hillen, Anne E J; Hruzova, Martina; Rothgangl, Tanja; Breur, Marjolein; Bugiani, Marianna; van der Knaap, Marjo S; Schwank, Gerald; Heine, Vivi M

doi:10.1016/j.omtm.2022.02.006

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Hillen, A. E. J., Hruzova, M., Rothgangl, T., Breur, M., Bugiani, M., van der Knaap, M. S., Schwank, G., & Heine, V. M. (2022). In vivo targeting of a variant causing vanishing white matter using CRISPR/Cas9. Molecular Therapy - Methods & Clinical Development, 25, 17–25. https://doi.org/10.1016/j.omtm.2022.02.006

Abstract

Vanishing white matter (VWM) is a leukodystrophy caused by recessive variants in subunits of eIF2B. At present, no curative treatment is available and patients often die at young age. Due to its monogenic nature, VWM is a promising candidate for the development of CRISPR/Cas9-mediated gene therapy. Here we tested a dual-AAV approach in VWM mice encoding CRISPR/Cas9 and a DNA donor template to correct a pathogenic variant in Eif2b5. We performed sequencing analysis to assess gene correction rates and examined effects on the VWM phenoty