Renovating Neural Networks With Viral‐Mediated Gene Transfer From A Tissue Contacting Matrix Mimic

Shiva Soltani Dehnavi; Negar Mahmoudi; Yi Wang; Samuel Cheeseman; Rita Ferreira; Ross D. Hannan; Leszek Lisowski; Vincent S. J. Craig; Niamh Moriarty; Clare L. Parish; Richard J. Williams; David R. Nisbet

doi:10.1002/smll.202510539

journal article·2026-03Open access

Renovating Neural Networks With Viral‐Mediated Gene Transfer From A Tissue Contacting Matrix Mimic

Shiva Soltani Dehnavi, Negar Mahmoudi, Yi Wang, Samuel Cheeseman, Rita Ferreira, Ross D. Hannan, Leszek Lisowski, Vincent S. J. Craig, Niamh Moriarty, Clare L. Parish, Richard J. Williams, David R. Nisbet

Small· Volume 22· Issue 17

Publisher page Open full text

Source abstract

Abstract

ABSTRACT Neurodegenerative diseases such as Huntington's Disease (HD) have a significant impact on healthcare accessibility and costs. A fatal genetic condition, characterized by the progressive loss of striatal neurons, HD is hindered by the lack of endogenous repair in the adult brain. Recent efforts toward protecting neural circuits through neurotrophic support using brain‐derived neurotrophic factor (BDNF) have been suboptimal due to the protein's short half‐life and limited diffusion. Addressing this, adeno‐associated viral vectors (AAV) can be employed as a delivery tool to spatially transduce cells, enabling the localised production of BDNF with consequential neuron protection and/or plasticity, yet present their own constraints. To overcome these known challenges of AAV gene delivery, an injectable, physiologically stable hydrogel‐mimic of the brain's extracellular matrix was fabricated to encapsulate the AAVs. This smart system both shielded and constrained the AAV; optimising transfection and therefore elevated and sustained BDNF presentation at the target site. Here, we achieved high neuroprotection using AAVDJ‐BDNF delivered through a hydrogel formed via self‐assembling peptide nanoscaffolds. These findings support the notion that the spatiotemporal release of BDNF to striatal neurons, facilitated by engineered biomaterial delivery systems, demonstrates tremendous promise by enhancing the efficacy of gene therapy targeted at slowing neurodegenerative disease progression.

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Research context

Polymers Nanomaterials Biomaterials

OpenAlex topics: Genetic Neurodegenerative Diseases · Nerve injury and regeneration · Neuroscience and Neural Engineering

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

ANU College of Engineering Computing, and Cybernetics Canberra Australian Capital Territory Australia

Genome Sciences and Cancer Division The John Curtin School of Medical Research ANU College of Health & Medicine Canberra Australian Capital Territory Australia

The Eccles Institute of Neuroscience The John Curtin School of Medical Research ANU College of Science & Medicine Canberra Australian Capital Territory Australia

Department of Biomedical Engineering Faculty of Engineering and Information Technology The University of Melbourne Melbourne Victoria Australia

The Graeme Clark Institute The University of Melbourne Melbourne Victoria Australia

Translational Vectorology Research Unit Children's Medical Research Institute Faculty of Medicine and Health The University of Sydney Sydney New South Wales Australia

Vector and Genome Engineering Facility Children's Medical Research Institute Faculty of Medicine and Health The University of Sydney Sydney New South Wales Australia

Australian Genome Therapeutics Centre Children's Medical Research Institute and Sydney Children's Hospitals Network Sydney Australia

Military Institute of Medicine Laboratory of Molecular Oncology and Innovative Therapies Warsaw Poland

Department of Materials Physics Research School of Physics Australian National University Canberra Australian Capital Territory Australia

The Florey Institute of Neuroscience and Mental Health The University of Melbourne Parkville Victoria Australia

iMPACT School of Medicine Deakin University Waurn Ponds Victoria Australia

Aikenhead Centre for Medical Discovery St. Vincent's Hospital Melbourne Victoria Australia

Melbourne Medical School Faculty of Medicine Dentistry and Health Science The University of Melbourne Melbourne Victoria Australia

Funding

Australian Research Council · National Health and Medical Research Council

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