Brief intro:
- Author: Wei-Ke Li, Shu-Qian Zhang, Wan-Ling Peng, Yu-Han Shi, Bo Yuan, Yi-Ting Yuan, Zhen-Yu Xue, Jin-Cheng Wang, Wen-Jian Han, Zhi-Fang Chen, Shi-Fang Shan, Bi-Qing Xue, Jin-Long Chen, Cheng Zhang, Shu-Jia Zhu, Yi-Lin Tai, Tian-Lin Cheng & Zi-Long Qiu
- Journal: Nature Neuroscience
- Doi: https://www.doi.org/10.1038/s41593-023-01499-x
- Publication Date: 2023 Nov 27
Products/Services used in the paper
Quotation shows PackGene:For sparse labeling to investigate neuronal spine development in vivo, the mixture of AAV-hSyn-Cre (0.05 μl of 1–1.25 × 1013 vg ml−1, generated by the Taitool Bioscience) and AAV-hSyn-DIO-tdTomato (0.05 μl of 2.9 × 1012 vg ml−1, generated by PackGene) was injected stereotactically into the bilateral mPFC of continuously anesthetized mice after glass pipette penetration. The stereotactic coordinates targeting the mPFC region were as followed: anteroposterior, +2.45 mm; mediolateral, 0.3 mm; dorsoventral, −1.0 mm. Mice were euthanized and perfused 1 month later after viral stereotactic injection. Subsequently, these two vectors were packaged into the AAV-PHP.eb virus by the PackGene Biotech and OBiO Corporation to efficiently infect neuronal cells in the brain by crossing the BBB.
Research Field:CNS
AAV Serotype:AAV-PHP.eb virus
Targeted organ:brain
Animal or cell line strain:mouse
Abstract
Whole-brain genome editing to correct single-base mutations and reduce or reverse behavioral changes in animal models of autism spectrum disorder (ASD) has not yet been achieved. We developed an apolipoprotein B messenger RNA-editing enzyme, catalytic polypeptide-embedded cytosine base editor (AeCBE) system for converting C·G to T·A base pairs. We demonstrate its effectiveness by targeting AeCBE to an ASD-associated mutation of the MEF2C gene (c.104T>C, p.L35P) in vivo in mice. We first constructed Mef2cL35P heterozygous mice. Male heterozygous mice exhibited hyperactivity, repetitive behavior and social abnormalities. We then programmed AeCBE to edit the mutated C·G base pairs of Mef2c in the mouse brain through the intravenous injection of blood–brain barrier-crossing adeno-associated virus. This treatment successfully restored Mef2c protein levels in several brain regions and reversed the behavioral abnormalities in Mef2c-mutant mice. Our work presents an in vivo base-editing paradigm that could potentially correct single-base genetic mutations in the brain.
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.
