Related Experiment Video
Updated: Sep 12, 2025
09:20
Isolation of Next-Generation Gene Therapy Vectors through Engineering, Barcoding, and Screening of Adeno-Associated Virus AAV Capsid Variants
Published on: October 18, 2022
4.7K
Barrier Function of the Extracellular Matrix in AAV Gene Therapy
Yahya Cheema1, Devorah Cahn1,2, Sahana Kumar1
1Fischell Department of Bioengineering, University of Maryland, College Park, MD 20742, USA.
Biorxiv : the Preprint Server for Biology
|August 6, 2025
Summary
Adeno-associated virus (AAV) transport and gene delivery can be hindered by the extracellular matrix (ECM). Understanding AAV-ECM interactions is crucial for effective AAV gene therapy development.
Area of Science:
- Biomedical Engineering
- Gene Therapy
- Extracellular Matrix Biology
Background:
- The extracellular matrix (ECM) significantly influences the tissue microenvironment.
- ECM can impede adeno-associated virus (AAV) distribution, limiting therapeutic gene delivery to target organs.
Purpose of the Study:
- To investigate the impact of AAV serotype and ECM composition on AAV transport and gene delivery.
- To elucidate AAV-ECM interactions to overcome potential barriers in AAV gene therapy.
Main Methods:
- Fluorescently labeled AAV2, AAV6, and AAV8 vectors were used to visualize diffusion in tissue-specific decellularized ECM (dECM) hydrogels.
- AAV and nanoparticle diffusion were quantified using fluorescent microscopy and particle tracking.
- AAV transduction efficiency was assessed in dECM-incorporated 2D and 3D spheroid models.
Main Results:
- All tested AAV serotypes exhibited reduced diffusivity in ECM compared to nanoparticles.
- AAV2 showed the least diffusion reduction across different ECM types, unlike AAV6 and AAV8.
- AAV transduction was significantly diminished in both 2D and 3D dECM-incorporated models.
Conclusions:
- AAV binding to the ECM may reduce therapeutic efficacy in target tissues.
- The barrier properties of the ECM must be considered during the development of AAV-based gene therapies.
