ORIGINAL RESEARCH article
Front. Med.
Sec. Gene and Cell Therapy
Volume 12 - 2025 | doi: 10.3389/fmed.2025.1672046
Efficient tau gene delivery via extracellular vesicles in Neuro-2a cells
Provisionally accepted
- 1Joint School of Nanoscience and Nanoengineering, Greensboro, United States
- 2North Carolina Agricultural and Technical State University, Greensboro, United States
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Tauopathy models are essential in vitro tools for investigating tau-targeted therapies and advancing Alzheimer's disease research. These models not only provide insights into disease mechanisms but also facilitate therapeutic development and drug screening. Extracellular vesicles (EVs), owing to their high biocompatibility, low toxicity, and reduced immunogenicity, are promising carriers for gene delivery and disease modeling. In this study, we hypothesized that EVs could serve as a versatile and effective system for tau gene delivery to generate a more biocompatible tauopathy model. We optimized EV-mediated delivery of human four-repeat tau lacking N-terminal sequences (4R0N) along with enhanced green fluorescent protein (EGFP) into Neuro-2a cells and compared its efficiency with conventional transfection methods, including lentiviral vectors and chemical reagents (lipofectamine and polyethyleneimine, PEI). Our results show that EVs successfully delivered large plasmid DNA into Neuro-2a cells, achieving detectable gene expression. Furthermore, we employed response surface methodology (RSM) to optimize the model, enhancing the efficiency and robustness of EV-mediated gene delivery. These findings highlight the potential of EVs as a biocompatible and robust alternative to traditional transfection approaches for tauopathy modeling.
Keywords: Transfection, gene delivery, Electroporation, Exosomes, EGFP
Received: 23 Jul 2025; Accepted: 29 Sep 2025.
Copyright: © 2025 Ghadami and Dellinger. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Kristen Dellinger, kdellinger@ncat.edu
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.