Adeno-associated viruses escort nanomaterials to specific cells and tissues
Nagao, K.; Vargas Paniagua, E.; Lei, K.; Beckham, J. L.; Worthington, P.; Manthey, M.; Ye, M.; Koehler, F.; Kim, Y. J.; Malkin, E.; Onoda, M.; Kent, N.; Michida, S.; Crespin Guerra, E.; Macfarlane, R. J.; Anikeeva, P.
Show 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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