# Developing and optimizing a biocompatible tauopathy model using extracellular vesicle-mediated gene delivery

## TL;DR

This study shows that extracellular vesicles can efficiently and safely deliver genes to create models for studying tau-related diseases like Alzheimer's.

## Contribution

The paper introduces an optimized, biocompatible method for gene delivery using extracellular vesicles for tauopathy modeling.

## Key findings

- EVs successfully delivered large plasmid DNA into Neuro-2a cells, resulting in detectable tau and EGFP expression.
- Optimization via RSM improved EV-mediated gene delivery efficiency and reproducibility over conventional methods.
- EVs offer a biocompatible and effective alternative to traditional transfection strategies for tauopathy models.

## Abstract

Tauopathy models are essential in vitro systems for investigating tau-targeted therapies and advancing Alzheimer’s disease research. Extracellular vesicles (EVs), owing to their high biocompatibility, low toxicity, and reduced immunogenicity, represent promising carriers for gene delivery and disease modeling.

We investigated the potential of EVs as a delivery system for the human four-repeat tau isoform lacking N-terminal sequences (4R0N) and enhanced green fluorescent protein (EGFP) into Neuro-2a cells. EV-mediated transfection efficiency was compared with conventional methods, including lentiviral and chemical (lipofectamine and polyethyleneimine, PEI) approaches. Response surface methodology (RSM) was used to optimize EV-mediated delivery parameters.

EVs successfully delivered large plasmid DNA into Neuro-2a cells, resulting in detectable tau and EGFP expression. Optimization via RSM further improved gene delivery efficiency and reproducibility compared to unoptimized EV preparations and conventional transfection methods.

These findings demonstrate that EVs can serve as a robust and biocompatible platform for tau gene delivery, providing a promising alternative to traditional transfection strategies for generating physiologically relevant tauopathy models.