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Beilstein Arch. 2021, 20217. https://doi.org/10.3762/bxiv.2021.7.v1
Published 26 Jan 2021
Lipid nanoparticles (LNPs) constitute a facile and scalable approach for delivery of payloads to human cells. LNPs are relatively immunologically inert and can be produced in a cost effective and scalable manner. However, targeting and delivery of LNPs across the blood brain barrier (BBB) has proven challenging. In an effort to target LNPs to particular cell types as well as generating LNPs that can cross the BBB, we developed and assessed two approaches whereby BBB penetrating peptides Tat or T7, and RNA aptamers targeted to gp160 from HIV or CCR5, a HIV-1 co-receptor, were incorporated into LNPs. We report here that a CCR5 selective RNA aptamer acts to facilitate entry through a simplified BBB model and to drive the uptake of LNPs into CCR5 expressing cells, while the gp160 aptamer did not. We further observed that the addition of cell penetrating peptides, Tat, did not increase BBB penetration above the aptamer loaded LNPs alone. Moreover, we find that these targeted LNPs exhibit low immunogenic and low toxic profiles and that targeted LNPs can traverse the BBB to potentially deliver drugs into the target tissue. This approach highlights the usefulness of aptamer loaded LNPs to increase target cell specificity and potentially, deliverability across the BBB.
Keywords: Lipid nanoparticle; aptamer; blood-brain-barrier; gene therapy; HIV-1
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Ray, R. M.; Hansen, A. H.; Taskova, M.; Jandl, B.; Hansen, J.; Soemardy, C.; Morris, K. V.; Astakhova, K. Beilstein Arch. 2021, 20217. doi:10.3762/bxiv.2021.7.v1
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