title: Induction of HIV-1 gag specific immune responses by cationic micelles mediated delivery of gag mRNA.
abstract: In recent years, mRNA-based vaccines have emerged to be a great alternative to DNA-based vaccines due to the safety of not inserting into host genome. However, mRNA molecules are single-stranded nucleic acids that are vulnerable under RNase existing in human skin and tissues. In this study, a self-assembled cationic nanomicelles based on polyethyleneimine-stearic acid (PSA) copolymer were developed to delivery HIV-1 gag encoding mRNA to dendritic cells and BALB/c mice. We evaluated the transfection efficiency and cell uptake efficiency of naked EGFP mRNA, PSA, PEI-2k and PEI-25k nanoparticles format on DC2.4 cell lines. Immune responses after sub-cutaneous administration of gag mRNA to BALB/c mice were notably induced by PSA as compared with naked gag mRNA. We found the PSA/mRNA nanomicelles were potent systems that can effectively deliver mRNA and induce antigen-specific immune response, stimulating various new vaccine strategies using mRNA.
authors.affiliation: a Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education , West China School of Pharmacy, Sichuan University , Chengdu , People's Republic of China.
authors.forename: Mengnan
authors.initials: M
authors.lastname: Zhao
authors.affiliation: a Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education , West China School of Pharmacy, Sichuan University , Chengdu , People's Republic of China.
authors.forename: Man
authors.initials: M
authors.lastname: Li
authors.affiliation: a Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education , West China School of Pharmacy, Sichuan University , Chengdu , People's Republic of China.
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: a Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education , West China School of Pharmacy, Sichuan University , Chengdu , People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Gong
authors.affiliation: a Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education , West China School of Pharmacy, Sichuan University , Chengdu , People's Republic of China.
authors.forename: Xun
authors.initials: X
authors.lastname: Sun
mesh_terms: D000818:Animals; D002412:Cations / Q000737:chemistry*; D003713:Dendritic Cells / Q000737:chemistry*; D015750:Genes, gag / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D015497:HIV-1 / Q000737:chemistry / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D012260:Ribonucleases / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D013229:Stearic Acids / Q000737:chemistry; D014162:Transfection; D014612:Vaccines / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism
chemical_list: D002412:Cations; D008823:Micelles; D012333:RNA, Messenger; D013229:Stearic Acids; D014612:Vaccines; C000616151:polyethyleneimine-stearic acid; D012260:Ribonucleases
keywords: Cationic polymers; HIV-1 gag; endosome escape; intracellular cytokine staining; messenger RNA