antisense pmo found in dystrophic dog model was effective in cells from exon 7-deleted dmd patient反义pmo瘠薄狗模型中发现有效的细胞外显子7-deleted dmd病人.pdfVIP

Antisense PMO Found in Dystrophic Dog Model Was Effective in Cells from Exon 7-Deleted DMD Patient 1,2 1 1 3 1 Takashi Saito , Akinori Nakamura , Yoshitsugu Aoki , Toshifumi Yokota , Takashi Okada , Makiko 2 1 Osawa , Shin’ichi Takeda * 1 Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan, 2 Department of Pediatrics, School of Medicine, Tokyo Women’s Medical University, Shinjuku, Tokyo, Japan, 3 Research Center for Genetic Medicine, Children’s National Medical Center, Washington, District of Columbia, United States of America Abstract Background: Antisense oligonucleotide-induced exon skipping is a promising approach for treatment of Duchenne muscular dystrophy (DMD). We have systemically administered an antisense phosphorodiamidate morpholino oligomer (PMO) targeting dystrophin exons 6 and 8 to a dog with canine X-linked muscular dystrophy in Japan (CXMDJ) lacking exon 7 and achieved recovery of dystrophin in skeletal muscle. To date, however, antisense chemical compounds used in DMD animal models have not been directly applied to a DMD patient having the same type of exon deletion. We recently identified a DMD patient with an exon 7 deletion and tried direct translation of the antisense PMO used in dog models to the DMD patient’s cells. Methodology/Principal Findings: We converted fibroblasts of CXMDJ and the DMD patient to myotubes by FACS-aided MyoD transduction. Antisense PMOs targeting identical regions of dog and human dystrophin exons 6 and 8 were designed. These antisens