Antisense-oligonucleotides (AS-ODNs) are not able to protect the bound ODN against degradation enzyme in biological fluids and be taken up by targeting cells. To solve these issues, the development of drug delivery systems to deliver AS-ODNs has been studied. We have studied a polysaccharide schizophyllan (denoted by SPG), a member of b-glucans, as a delivery carrier of oligonucleotides. SPG can form a complex with polydeoxyadenosine (denoted by dA base numbers) and prevents degradation by enzymes. We have reported that the complex comprising of SPG and the dA40 that was beforehand connected with AS-ODNs (AS-ODN-dA40). The complex can deliver AS-ODNs to dectin-1-expresseing cell and silence mRNA, then, eventually suppress protein expressions. TAT peptide: human immunodeficiency virus type 1 protein fragments is known one of the major arginine-rich cell penetrating peptides. We prepared TAT peptide conjugate phosphorothioate dA40 oligonucleotide (denoted by TAT-dA40) by the click chemistry reaction. The TAT-dA40/AS-yb-1-dA40/SPG complexes showed a higher cell uptake and more cell-growth suppression than AS-yb-1-dA40/SPG complex that had not TAT. We suppose that this improvement can be ascribed to TAT-induced cellular ingestion of the complexes.

B-glucan/ODN carrier conjugated with TAT peptide: Specific delivery to cytosol

251st National Meeting (2016)

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