简介:
- 作者: 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
- 杂志: Nature Neuroscience
- Doi: https://www.doi.org/10.1038/s41593-023-01499-x
- 出版日期: 2023 Nov 27
论文中使用的产品/服务
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
摘要
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.
关于派真
作为一家专注于AAV 技术十余年，深耕基因治疗领域的CRO&CDMO，派真生物可提供从载体设计、构建到 AAV、慢病毒和 mRNA 服务的一站式解决方案。凭借深厚的技术实力、卓越的运营管理和高标准的服务交付，我们为全球客户提供一站式CMC解决方案，包括从早期概念验证、成药性评估到IIT、IND及BLA的各个阶段。
凭借我们独立知识产权的π-alphaTM 293 细胞AAV高产技术平台，我们能将AAV产量提高多至10倍，每批次产量可达1×10¹⁷vg，以满足多样化的商业化和临床项目需求。此外，我们定制化的mRNA和脂质纳米颗粒（LNP）产品及服务覆盖药物和疫苗开发的各个阶段，从研发到符合GMP的生产，提供端到端的一站式解决方案。
