Aptamer-conjugated gold nanoparticles enable oligonucleotide delivery into muscle stem cells to promote regeneration of dystrophic muscles
Inefficient targeting of muscle stem cells (MuSCs), also called satellite cells, represents a major bottleneck of current therapeutic strategies for muscular dystrophies, as it precludes the possibility of promoting compensatory regeneration. Here we describe a muscle-targeting delivery platform, based on gold nanoparticles, that enables the release of therapeutic oligonucleotides into MuSCs. We demonstrate that AuNPs conjugation to an aptamer against α7/β1 integrin dimers directs either local or systemic delivery of microRNA-206 to MuSCs, thereby promoting muscle regeneration and improving muscle functionality, in a mouse model of Duchenne Muscular Dystrophy. We show here that this platform is biocompatible, non-toxic, and non-immunogenic, and it can be easily adapted for the release of a wide range of therapeutic oligonucleotides into diseased muscles.
Authors
- Álvaro Somoza (ORCID: https://orcid.org/0000-0001-9873-435X)
- Paula Milán-Rois (ORCID: https://orcid.org/0000-0002-7043-2920)
- Daniela Palacios (ORCID: https://orcid.org/0000-0002-2207-2369)
- Arghya Sett (ORCID: https://orcid.org/0000-0002-8356-5140)
- Federica Esposito (ORCID: https://orcid.org/0000-0001-6732-5756)
- Marina Bouché (ORCID: https://orcid.org/0000-0002-0938-5360)
- Ciro Rodríguez Díaz (ORCID: https://orcid.org/0000-0002-8271-2495)
- Miguel Gisbert-Garzarán (ORCID: https://orcid.org/0000-0001-9815-0354)
- Martina Sandonà (ORCID: https://orcid.org/0000-0001-9639-9041)
- Jean‐Jacques Toulmé (ORCID: https://orcid.org/0000-0002-8432-5034)
- Marco De Bardi (ORCID: https://orcid.org/0000-0001-8217-970X)
- Ornella Parolini (ORCID: https://orcid.org/0000-0002-5211-6430)
- Valentina Saccone (ORCID: https://orcid.org/0000-0002-0566-6384)
- Giovanni Delli Carpini (ORCID: https://orcid.org/0000-0003-2849-4690)
- Mario Martínez‐Mingo (ORCID: https://orcid.org/0000-0002-2963-5769)
- Francesco Millozzi (ORCID: https://orcid.org/0000-0002-2737-4251)
- Maria Teresa Viscomi (ORCID: https://orcid.org/0000-0002-9096-4967)
- Irene Pardo (ORCID: https://orcid.org/0009-0004-9237-7936)
Institutions
- Università Cattolica del Sacro Cuore (IT)
- Madrid Institute for Advanced Studies (ES)
- Centre National de la Recherche Scientifique (FR)
- Optech (Canada) (CA)
- Inserm (FR)
- Agostino Gemelli University Polyclinic (IT)
- Centro Nacional de Biotecnología (ES)
- Bordeaux Population Health (FR)
- Luxembourg Institute of Science and Technology (LU)
- Institute for Systems Analysis (RU)
- Fondazione Santa Lucia (IT)
- Istituti di Ricovero e Cura a Carattere Scientifico (IT)
- National Research Council (IT)
- Istituto di Analisi dei Sistemi ed Informatica Antonio Ruberti (IT)
- Sapienza University of Rome (IT)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-01-10
- DOI
- https://doi.org/10.1038/s41467-024-55223-9
- Citations
- 22
- Primary Topic
- RNA Interference and Gene Delivery
- Type
- article
- Field-Weighted Citation Impact
- 17.73
Funders
- Association Française contre les Myopathies
- Comunidad de Madrid
- Ministerio de Economía y Competitividad
- Ministerio de Ciencia e Innovación
- Università Cattolica del Sacro Cuore
- Horizon 2020 Framework Programme