Diagenode

Long-term evaluation of AAV-CRISPR genome editing for Duchenne muscular dystrophy.


Nelson CE, Wu Y, Gemberling MP, Oliver ML, Waller MA, Bohning JD, Robinson-Hamm JN, Bulaklak K, Castellanos Rivera RM, Collier JH, Asokan A, Gersbach CA

Duchenne muscular dystrophy (DMD) is a monogenic disorder and a candidate for therapeutic genome editing. There have been several recent reports of genome editing in preclinical models of Duchenne muscular dystrophy, however, the long-term persistence and safety of these genome editing approaches have not been addressed. Here we show that genome editing and dystrophin protein restoration is sustained in the mdx mouse model of Duchenne muscular dystrophy for 1 year after a single intravenous administration of an adeno-associated virus that encodes CRISPR (AAV-CRISPR). We also show that AAV-CRISPR is immunogenic when administered to adult mice; however, humoral and cellular immune responses can be avoided by treating neonatal mice. Additionally, we describe unintended genome and transcript alterations induced by AAV-CRISPR that should be considered for the development of AAV-CRISPR as a therapeutic approach. This study shows the potential of AAV-CRISPR for permanent genome corrections and highlights aspects of host response and alternative genome editing outcomes that require further study.

Tags
CRISPR

Share this article

Published
March, 2019

Source

Products used in this publication

  • Antibody cas9 icon
    C15200230-100
    S. aureus CRISPR/Cas9 monoclonal antibody

         Site map   |   Contact us   |   Conditions of sales   |   Conditions of purchase   |   Privacy policy   |   Diagenode Diagnostics