Enhanced target cell specificity and uptake of lipid nanoparticles using RNA aptamers and peptides

• Roslyn M. Ray,
• Anders Højgaard Hansen,
• Maria Taskova,
• Bernhard Jandl,
• Jonas Hansen,
• Citra Soemardy,
• Kevin V. Morris and
• Kira Astakhova

Beilstein J. Org. Chem. 2021, 17, 891–907, doi:10.3762/bjoc.17.75

• the usefulness of aptamer-loaded LNPs to increase target cell specificity and potentially deliverability of central-nervous-system-active RNAi therapeutics across the BBB. Keywords: aptamer; blood–brain barrier; gene therapy; HIV-1; lipid nanoparticle; Introduction Lipid nanoparticles (LNPs

• low immunogenic and toxic profile and that RNA aptamers can act as potential enhancers to effectuate the delivery of LNPs into the central nervous system (CNS). Results Lipid nanoparticle development and characteristics In accordance with a previously published procedure, we generated LNPs using a

• . Lipid nanoparticle synthesis The formulation protocol was largely adapted from Jayaraman et al. (2012) [4]. Freshly prepared lipid stocks (in chloroform) were mixed to obtain the desired mole fractions (DLin-MC3-DMA/DSPC/Cholesterol/DMG-PEG 2000 0.4:0.1:0.4:0.1), and the lipid mixture was concentrated