National Center for Neurology and Phychiatry Department of Molecular Therapy, National Institute of Neuroscience


Genetic Therapy Group (Exon Skipping)


Led by Yoshitsugu AOKI, MD, PhD, our research group focuses on fatal Duchenne muscular dystrophy and other neuromuscular diseases. Our lab integrates molecular, pharmacologic, proteomic and genomic methodologies to clarify the molecular mechanisms of disease pathogenesis and develop novel genetic therapies for the diseases.

Oligonucleotide-based Exon Skipping for Duchenne Muscular Dystrophy

A major focus of our group concerns the development of single- and multi-exon skipping therapy for Duchenne muscular dystrophy, with the intention of increasing our understanding of the pathogenesis in this disease and translating this understanding into improved therapies. Recently, a proof of concept for systemic single exon 51-skipping (Molecular Therapy 2010) and exons 45-55 skipping by targeting ten exons have been provided in dystrophic mice (PNAS 2012, Human Molecular Genetics 2013) in collaboration with Yokota lab, University of Alberta. Other projects in the lab are dedicated to the development of novel oligonucleotide delivery to the muscle and the brain in collaboration with Dr. Shabanpoor, University of Melbourne.

Cellular Uptake Mechanism of Oligonucleotides in Dystrophinopathy

In addition to medical research, our lab is interested in basic science projects including the cellular uptake mechanism of oligonucleotide. We have recently demonstrated an innovative work (Nano Letters 2015) to state that self-assembly of nanoparticles is essential for receptor-mediated uptake of the peptide-conjugated morpholino antisense oligo in collaboration with Wood lab, University of Oxford ( Currently, the cellular uptake mechanisms of oligonucleotides in living cells is further examined by using proteomic analysis in collaboration with Andaloussi lab, Karolinska Institutet.

Extracellular and Intracellular Vesicle Trafficking in Neuromuscular Diseases

Our lab is also interested in the biogenesis of extracellular vesicles and intercellular communication. To date, we have discovered a fundamentally disturbed molecular pathway in C9orf72-related amyotrophic lateral sclerosis (ALS) and frontotemporal dementia that identifies a novel extracellular vesicle trafficking, determines the molecular mechanisms and for the first time links ALS pathogenesis with extracellular vesicle biogenesis (under the revision).
The goal of the laboratory is a better understanding and improved treatment of fatal and currently untreated neuromuscular diseases.