1 Department of Pathology, University of Otago , Dunedin, New Zealand .
2 Department of Chemistry, University of Otago , Dunedin, New Zealand .
Nucleic Acid Ther. 2018 Aug;28(4):225-232. doi: 10.1089/nat.2017.0695. Epub 2018 Jun 12.
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.
MIS416 是一种源自痤疮丙酸杆菌细胞壁骨架的微粒制剂,具有内在的佐剂活性。含有二硫键的 MIS416-SS-肽缀合物有助于将肽递送至抗原呈递细胞 (APC) 并在其中释放。我们假设,含有 MIS416 和 siRNA 之间二硫键的 MIS416-siRNA(小干扰 RNA)缀合物将允许 siRNA 在 APC 中细胞质释放。MIS416-SS-siStat3 缀合物添加到培养瓶中单细胞层 DC 的细胞培养基中,成功地在体外靶向 DC 中的 Stat3 mRNA,而无需转染,从而下调 Stat3 mRNA 和蛋白水平。这些结果表明,MIS416-SS-siRNA 缀合物可用作新型 siRNA 递药系统,用于敲低 APC 中的 mRNA 水平。