Long-term comparative analysis of AAV9-mediated gene replacement therapies for spinal muscular atrophy in mice
Xiupeng Chen·Jun Xie·Sarah J. Nath·Mojiao Tang·Hong Ma·Yasemin Özgür Günes·Tapan Sharma·Hao Liu·Mengtian Cui·Ailing Du·Mengjia Lu·Sophia Y. Liu·Boonying Wassamon·Mengyao Xu·Joseph Yunxi Wu·Qin Su·Timothy P. Fitzgibbons·Jinghua Liu·Fang Wan·Veena Kumanan·Ran He·Yijie Ma·Jun Yang·Heather Gray‐Edwards·Thomas L. Gallagher·Phillip W.L. Tai·Guangping Gao·Qing Xie
Abstract Spinal muscular atrophy (SMA) results from a deficiency of the survival motor neuron (SMN) protein. Zolgensma, an adeno-associated virus (AAV)-based SMN1 gene-replacement therapy, is approved for SMA, though its long-term efficacy and safety remain uncertain. This study compares a Zolgensma-like benchmark vector with a 2nd-generation vector featuring a codon-optimized SMN1 transgene under the control of an endogenous SMN1 promoter. In SMA mice, intracerebroventricular delivery of the 2n