Dongsheng Duan

Dongsheng Duan, Ph.D., is Curators' Distinguished Professor and Margaret Proctor Mulligan Professor in Medical Research at the University of Missouri School of Medicine, with appointments in the Departments of Molecular Microbiology and Immunology, Neurology, Biomedical Sciences (College of Veterinary Medicine), and Chemical and Biomedical Engineering (College of Engineering). He is a Fellow of the National Academy of Inventors and the American Association for the Advancement of Science. Dr. Duan is internationally recognized as a pioneering leader in adeno-associated virus (AAV) micro-dystrophin gene therapy for Duchenne muscular dystrophy (DMD), a lethal muscle disease caused by dystrophin gene mutations. The enormous size of the dystrophin gene (~11kb coding sequence) exceeds AAV packaging capacity (~4.7kb). Duan, collaborating with colleagues including Xiao Xiao, pioneered micro-dystrophin technology—highly abbreviated dystrophin variants retaining critical functional domains that fit within AAV vectors. In 2008, the Duan laboratory demonstrated that systemic AAV9 transduction was effective in canine models (golden retriever muscular dystrophy, GRMD), establishing proof-of-concept for body-wide DMD gene delivery. Duan's laboratory has made seminal contributions to dystrophin structural biology, discovering multiple independent membrane-binding domains beyond the previously known cysteine-rich domain (2016 Human Molecular Genetics). This work guided rational design of optimized micro-dystrophin constructs. His 2018 Molecular Therapy review "Systemic AAV Micro-dystrophin Gene Therapy for Duchenne Muscular Dystrophy" serves as the field's authoritative reference, systematically presenting how preclinical data demonstrated that AAV micro-dystrophin delivery can ameliorate muscle pathology, enhance muscle force, and attenuate dystrophic cardiomyopathy in animal models. The 2023 Science Translational Medicine publication reported results from a blinded, placebo-controlled study in GRMD dogs, demonstrating dose-dependent improvements in tissue transduction, muscle function, and histopathology, providing critical evidence that systemic AAV-microdystrophin may be dosed safely with therapeutic benefit for DMD patients. This work directly catalyzed clinical trials including Solid Biosciences' SGT-001 program, where Duan serves as scientific advisor. Duan's recent work includes CRISPR gene editing approaches for DMD, with his 2024 research identifying and overcoming key barriers in CRISPR editing to enable sustained treatments. He has secured over $30 million in NIH funding since joining the University of Missouri in 2002 and has authored over 150 peer-reviewed publications. He received the 2006 ASGCT Outstanding New Investigator Award and multiple University of Missouri honors including the 2009 Chancellor's Award for Outstanding Research.

Dongsheng Duan哲学博士，是密苏里大学医学院校董杰出教授和Margaret Proctor Mulligan医学研究教授，在分子微生物学与免疫学系、神经学系、生物医学科学系（兽医学院）和化学与生物医学工程系（工程学院）任职。他是美国发明家学会和美国科学促进会会士。 Duan博士国际公认为杜氏肌营养不良(DMD)腺相关病毒(AAV)微肌营养不良蛋白基因治疗的开创性领导者，DMD是一种由肌营养不良蛋白基因突变引起的致命肌肉疾病。肌营养不良蛋白基因的巨大尺寸（约11kb编码序列）超过了AAV包装容量（约4.7kb）。Duan与包括Xiao Xiao在内的同事合作，开创了微肌营养不良蛋白技术——高度缩写的肌营养不良蛋白变体，保留了适合AAV载体的关键功能域。2008年，Duan实验室证明系统性AAV9转导在犬模型（金毛寻回犬肌营养不良，GRMD）中有效，为全身DMD基因递送建立了概念验证。 Duan实验室在肌营养不良蛋白结构生物学方面做出了开创性贡献，发现了除先前已知的富半胱氨酸域之外的多个独立膜结合域（2016年Human Molecular Genetics）。这项工作指导了优化微肌营养不良蛋白构建的理性设计。他2018年在Molecular Therapy上的综述"杜氏肌营养不良的系统性AAV微肌营养不良蛋白基因治疗"是该领域的权威参考，系统地展示了临床前数据如何证明AAV微肌营养不良蛋白递送可以改善肌肉病理、增强肌力和减轻动物模型中的肌营养不良性心肌病。 2023年Science Translational Medicine出版物报告了GRMD犬盲法安慰剂对照研究的结果，证明组织转导、肌肉功能和组织病理学的剂量依赖性改善，提供了系统性AAV-微肌营养不良蛋白可以安全给药并为DMD患者带来治疗益处的关键证据。这项工作直接催化了包括Solid Biosciences的SGT-001项目在内的临床试验，Duan担任科学顾问。 Duan最近的工作包括DMD的CRISPR基因编辑方法，他2024年的研究识别并克服了CRISPR编辑中的关键障碍，以实现持续治疗。自2002年加入密苏里大学以来，他已获得超过3000万美元的NIH资助，并发表了150多篇同行评审出版物。他获得了2006年ASGCT杰出新研究者奖和多个密苏里大学荣誉，包括2009年校长杰出研究奖。