Carrier-free micellar CpG interacting with cell membrane for enhanced immunological treatment of HIV-1. (October 2021)

• Record Type: Journal Article
• Authors: Kim, Haejoo; Zhang, Wei; Hwang, Juyoung; An, Eun-Koung; Choi, Yeol Kyo; Moon, Eunyoung; Loznik, Mark; Huh, Yang Hoon; Herrmann, Andreas; Kwak, Minseok; Jin, Jun-O
• Is Part Of: Biomaterials. Volume 277(2021)
• Publication Date: 2021-10
• Subjects: DNA nanotechnology -- DNA micelles -- Dendritic cells -- Natural killer cells -- Anti-HIV; Biomedical materials -- Periodicals; Biocompatible Materials -- Periodicals; Biomatériaux -- Périodiques; 610.28
• DOI: 10.1016/j.biomaterials.2021.121081
• Languages: English
• ISSNs: 0142-9612

Abstract

Abstract: Unmethylated CpG motifs activate toll-like receptor 9 (TLR9), leading to sequence- and species-specific immune stimulation. Here, we engineered a CpG oligodeoxyribonucleotide (ODN) with multiple hydrophobic moieties, so-called lipid-modified uracil, which resulted in a facile micelle formation of the stimulant. The self-assembled CpG nanostructure (U4CpG) containing the ODN 2216 sequence was characterized by various spectroscopic and microscopic methods together with molecular dynamics simulations. Next, we evaluated the nano-immunostimulant for enhancement of anti-HIV immunity. U4CpG treatment induced activation of plasmacytoid dendritic cells (pDCs) and natural killer (NK) cells in healthy human peripheral blood, which produced type I interferons (IFNs) and IFN-γ in human peripheral blood mononuclear cells (PBMCs). Moreover, we validated the activation and promotion efficacy of U4CpG in patient-derived blood cells, and HIV-1 spread was significantly suppressed by a low dosage of the immunostimulant. Furthermore, U4CpG-treated PBMC cultured medium elicited transcription of latent HIV-1 in U1 cells indicating that U4CpG reversed HIV-1 latency. Thus, the functions of U4CpG in eradicating HIV-1 by enhancing immunity and reversing latency make the material a potential candidate for clinical studies dealing with viral infection. Graphical abstract: Image 1