Adeno-associated viruses escort nanomaterials to specific cells and tissues
Keisuke NagaoiD, Emmanuel Vargas Paniagua, Katherine LeiiD, Jacob L. BeckhamiD, Peyton Worthington, Marie Manthey, Matthew YeiD, Florian KoehleriD, Ye Ji KimiD, Elian Malkin, Michika OnodaiD, Noah KentiD, Shota Michida, Emily Crespin Guerra, Robert J. MacfarlaneiD, Polina AnikeevaiD
Abstract
The delivery of nanotherapeutics to specific tissues relies on bespoke targeting strategies or invasive surgeries. Conversely, adeno-associated viruses (AAVs) can target specific tissues following intravenous injections. Here we show that cell-targeting properties of AAVs could be broadly conferred to nanomaterials. We develop a strategy to couple AAV capsids to nanoparticles that is invariant of viral serotype or nanomaterial chemistry and permits control over stoichiometry of the AAV-nanoparticle chimeras. The chimeras selectively escort nanoparticles into cell classes governed by AAV serotypes. When applied to magnetic nanoparticles, the AAV-nanoparticle chimeras enable magnetically localized gene delivery. In vivo, we show that leveraging the brain-targeting AAV serotype CAP-B10 achieves nanoparticle delivery to the parenchyma with [~]10% efficiency (% injected dose/g[brain]) while avoiding accumulation in the liver. The enhanced delivery efficiency and tissue specificity highlight the potential of AAV-chimeras as a versatile strategy to escort broad classes of nanotherapeutics to the brain and beyond.
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