ORCID Profile
0000-0003-4878-0301
Current Organisations
University of California, San Diego
,
Technical University of Denmark
,
Copenhagen Business School
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Publisher: Elsevier BV
Date: 09-2019
Publisher: American Chemical Society (ACS)
Date: 04-01-2018
Publisher: Beilstein Institut
Date: 26-04-2021
DOI: 10.3762/BJOC.17.75
Abstract: 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 composed of an ionizable cationic lipid (DLin-MC3-DMA), cholesterol, the phospholipid 1,2-distearoyl- sn -glycero-3-phosphocholine (DSPC), and 1,2-dimyristoyl- rac -glycero-3-methoxypolyethylene glycol-2000 (DMG-PEG 2000) to particular cell types, as well as to generate LNPs that can cross the BBB, we developed and assessed two approaches. The first was centered on the BBB-penetrating trans-activator of transcription (Tat) peptide or the peptide T7, and the other on RNA aptamers targeted to glycoprotein gp160 from human immunodeficiency virus (HIV) or C-C chemokine receptor type 5 (CCR5), a HIV-1 coreceptor. We report herein a CCR5-selective RNA aptamer that acts to facilitate entry through a simplified BBB model and that drives 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 and T7, did not increase BBB penetration above the aptamer-loaded LNPs alone. Moreover, we found 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 of central-nervous-system-active RNAi therapeutics across the BBB.
Location: United States of America
Location: United States of America
Location: Russian Federation
Location: Russian Federation
No related grants have been discovered for Kira Astakhova.