MIS416 as a siRNA Delivery System with the Ability to Target Antigen-Presenting Cells

被引:3
作者
Mainini, Francesco [1 ]
Larsen, David S. [2 ]
Webster, Gill A. [3 ]
Young, Sarah L. [1 ,4 ]
Eccles, Michael R. [1 ,4 ]
机构
[1] Univ Otago, Dept Pathol, 56 Hanover St,9016, Dunedin 9054, New Zealand
[2] Univ Otago, Dept Chem, Dunedin, New Zealand
[3] Innate Immunotherapeut Ltd, Penrose, New Zealand
[4] Maurice Wilkins Ctr Mol Biodiscovery, Auckland, New Zealand
关键词
dendritic cells; Stat3; siRNA; gene silencing; delivery; DENDRITIC CELLS; VACCINE EFFICACY; IMMUNE TOLERANCE; CANCER; STAT3; SURVIVAL; NANOPARTICLES; ACTIVATION; RECEPTOR; THERAPY;
D O I
10.1089/nat.2017.0695
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
MIS416 is a microparticulate formulation derived from propionibacterium acnes cell wall skeletons with intrinsic adjuvant activity. Conjugates of MIS416-SS-peptide containing a disulfide linkage facilitate the cytoplasmic delivery and release of peptides in antigen-presenting cells (APCs). We hypothesized that MIS416-siRNA (small interfering RNA) conjugates, containing a disulfide linkage between MIS416 and the siRNA, would allow cytoplasmic release of siRNA in APCs. MIS416-SS-siStat3 conjugates added to cell culture medium of monolayers of DCs in culture flasks successfully targeted Stat3 mRNA in DCs in vitro without transfection, downregulating Stat3 mRNA and protein levels. These results suggest that MIS416-SS-siRNA conjugates can be used as a novel siRNA delivery system for the knockdown of mRNA levels in APCs.
引用
收藏
页码:225 / 232
页数:8
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