We found that a β-1,3-glucan schizophyllan (SPG) forms a macromolecular complex with single chain homo-polynucleotides, including poly deoxyadenine [poly(dA)]. β-1,3-glucans can bind to a lectin called Dectin-1 expressed on several immunocytes and the SPG/poly(dA) complex also bind to Dectin-1. By use of this recognition, antisense oligonucleotides that have a poly(dA) tail can be specifically deliver to immunocytes to downregulate a target protein. It has been reported that human dectin-1 has eight splice variants. In this study, we cloned human Dectin-1 variants and prepared the transfectants, and evaluated which variant show affinity to the SPG/DNA complex. Among the eight splice variants, we chose the six types of Dectin-1 containing the carbohydrate recognition domain and prepared the transfectants for PC3 cells which is a prostate cancer cell. Treatment with SPG/YB-1-antisence complexes induced the downregulation of YB-1 expression for the cells with variant 1, 2, 3 and 4, resulting in the suppression of cell growth, where YB-1 is a Y-box-binding protein. Especially, in the cells with variants1, 3, and 4 having stalk region, the complexes strongly inhibited the gene expression of YB-1 and cancer cell growth. Variant1, 3 and 4 also have N-glycosylation site. These findings suggest that a stalk region plays an important role in not only cellular uptake of the complex but also expression on the cell surface.

Dectin-1 targeting delivery of a therapeutic oligonucleotide with a beta-1,3-glucan carrier for cancer treatment

254th National Meeting (2017)

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