Bioengineering novel AAV9-mGULO-GT for multi-disease gene therapy: Targeting mutated GULO expression to cure scurvy and brain diseases
Brief intro:
- Author: 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
- Journal: Research Square
- Doi: https://www.doi.org/10.21203/rs.3.rs-3028525/v1
- Publication Date: 2023 Jun 23
Abstract
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.
About PackGene
PackGene Biotech is a world-leading CRO and CDMO, excelling in AAV vectors, mRNA, plasmid DNA, and lentiviral vector solutions. Our comprehensive offerings span from vector design and construction to AAV, lentivirus, and mRNA services. With a sharp focus on early-stage drug discovery, preclinical development, and cell and gene therapy trials, we deliver cost-effective, dependable, and scalable production solutions. Leveraging our groundbreaking π-alpha 293 AAV high-yield platform, we amplify AAV production by up to 10-fold, yielding up to 1e+17vg per batch to meet diverse commercial and clinical project needs. Moreover, our tailored mRNA and LNP products and services cater to every stage of drug and vaccine development, from research to GMP production, providing a seamless, end-to-end solution.
