Research Square. 2023 Jun 23
Jing Liu, Manish Kumar, Jing Guo, Luyuan Huang, Zhen Zhang, Yaofeng WANG, Rongping Luo, shilong chu, Shuyan Chen, Rongrong Liu, Jinjin Yu, Runxia Lin, shengyong yu, chunhua zhou, Jinpeng Liu, Yusha Li, Pratteek Das, Jitian Zhang, Yi Li, Ping Zhu, Duanqing Pei
Products used in the paper Details Operation
plasmid construction The mouse GULO gene (mGULO_NM_178747.3) was synthesized by PackGene Biotech (Guangzhou, China). The gene was driven by a CAG promoter, and the entire expression cassette was inserted between AAV2 inverted terminal repeats to create the transfer plasmid. In a similar manner, the luciferase gene was assembled to serve as a control for AAV infection. This construction allowed for efficient expression of the mGULO gene within the AAV vector. Request Quote

Research Field: Vitamin C deficiency

Keywords: AAV-mediated gene therapy, Guinea pig models, GULO gene, Tissue specicity, Vitamin Cdeciency

AAV Serotype: AAV9

Dose: 1E+13GC/m

Routes of Administration: intrasplenic infusion

Targeted organ: whole brain, spleen, heart, bone marrow, liver, thymus, lung, small intestine, large intestine, kidney, ovary, mid brain, brain stem, subcortical brain, anterior cerebral cortex, cerebellum brain, hippocampus brain and cerebral cortex

Animal or cell line strain: Juvenile sound guinea pigs (Hartley endure) 11 days of same age and weight were utilized for AAV9 injections.


Current clinical breakthroughs in gene therapy have brought adeno-associated virus (AAV) vectors to the forefront of gene delivery systems. Vitamin C deficiency due to GULO mutations is a genetic disorder affecting guinea pigs and humans. In our study, we used AAV9-mGULO-GT to deliver the mouse GULO gene to guinea pigs and restore Vc synthesis in affected tissues, including the liver and brain. AAV9-mGULO-GT treatment significantly improved survival rates and bone health compared to non-treated and Vc-treated groups. Dot blot analysis confirmed restored Vc content in various parts of the brain. Additionally, micro-CT imaging showcased significant enhancements in bone mineral density, content, width, and cortical thickness. Further, RNA sequencing and immunological studies of organs validated the successful restoration of Vc synthesis. These findings highlight the potential of AAV9-mGULO-GT as a therapeutic option for GULO-related scurvy and other genetic disorders. The success of our study underscores the importance of advanced targeting and gene rescue systems in developing effective therapies for genetic disorders in clinical applications.

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