Enhancer AAVs for targeting spinal motor neurons and descending motor pathways in rodents and macaque
简介:
- 作者: Emily Kussick, Nelson Johansen, Naz Taskin, Brooke Wynalda, Refugio Martinez, Erin L. Groce, Melissa Reding, Elizabeth Liang, Lyudmila Shulga, Cindy Huang, Tamara Casper, Michael Clark, Windy Ho, Yuan Gao, Cindy T.J. van Velthoven, Cassandra Sobieski, Rebecca Ferrer, Melissa R. Berg, Britni C. Curtis, Chris English, Jesse C. Day, Michal Fortuna, Nicholas Donadio, Dakota Newman, Shenqin Yao, Anish Bhaswanth Chakka, Jeff Goldy, Amy Torkelson, Junitta B. Guzman, Rushil Chakrabarty, Beagen Nguy, Nathan Guilford, Trangthanh H. Pham, Vonn Wright, Kara Ronellenfitch, Kathryn Gudsnuk, Bargavi Thyagarajan, Kimberly A. Smith, Nick Dee, Hongkui Zeng, Zizhen Yao, Bosiljka Tasic, Boaz P. Levi, Rebecca Hodge, Trygve E. Bakken, Ed S. Lein, Jonathan T. Ting and Tanya L. Daigle
- 杂志: BioRxiv
- Doi: https://www.doi.org/10.1101/2024.07.30.605864
- 出版日期: 2024 Jul 31
论文中使用的产品/服务
Quotation shows PackGene:For injections into macaque, large scale purified viral vector preps were packaged of the PHP.eB serotype by a commercial source (Packgene, Houston TX).
Research Field:spinal motor neurons
AAV Serotype:PHP.eB
Targeted organ:spinal motor neurons
Animal or cell line strain:mice, rat, macaque
摘要
Experimental access to cell types within the mammalian spinal cord is severely limited by the availability of genetic tools. To enable access to lower motor neurons (LMNs) and LMN subtypes, which function to integrate information from the brain and control movement through direct innervation of effector muscles, we generated single cell multiome datasets from mouse and macaque spinal cords and discovered putative enhancers for each neuronal population. We cloned these enhancers into adeno-associated viral vectors (AAVs) driving a reporter fluorophore and functionally screened them in mouse. The most promising candidate enhancers were then extensively characterized using imaging and molecular techniques and further tested in rat and macaque to show conservation of LMN labeling. Additionally, we combined enhancer elements into a single vector to achieve simultaneous labeling of upper motor neurons (UMNs) and LMNs. This unprecedented LMN toolkit will enable future investigations of cell type function across species and potential therapeutic interventions for human neurodegenerative diseases.
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。
