A Novel Polysaccharide Carrier for Functional Oligonucleotides: APS Targeting DDS with Dectin-1
Oligonucleotides (ODNs) are easily decomposed in biological fluids, which makes it difficult to administrate antisense DNA or CpG motif in a naked state. Cationic compounds have been used as a carrier for ODNs; however, they have drawbacks in cytotoxicity and selectivity in cellular or organ targeting. Schizophyllan (SPG) is a natural b-(1→3)-D-glucan existing as a triple helix in water and as a single chain in alkaline solutions, respectively. When homo-polynucleotides such as poly(dA) are added to SPG alkaline solution and subsequently pH is adjusted to be neutral, the single chain of SPG forms a stoichiometric complex with the polynucleotide. The complex can protect the bound DNA against nuclease-mediated hydrolysis or non-specific binding to serum proteins. Furthermore, recent immunology revealed that activated antigen presenting cells (APCs) including dendritic immune cells express a receptor called Dectin-1. We have demonstrated that Dectin-1 recognizes SPG/ODN complexes, and the complex is eventually ingested by APCs. This finding suggests that SPG/ODN complex can be specifically ingested by activated APCs and the bond ODN can exert its effect after ingestion. The present talk will show our recent in-vivo and vitro studies to prove this idea and provide a new strategy to specifically transport functional ODNs including antisense-DNA, CpG-DNA, and siRNA to APCs to cure the diseases due to disorientation of the immune system.
Director of Biomedical Material Center, Institute of Environmental Science and Technology (IEST), Department of Chemistry and Biochemistry, University of Kitakyushu, Japan
Kazuo Sakurai was born in 1958 in Gifu, Japan, and after nishing the master course of Osaka University, he joined Kanebo Ltd in 1984.
He spent three years (1990-1993) in the USA working for Professor William MacKnight at the University of Massachusetts, and received
his PhD from Osaka University in 1996. He worked for Professor Sinkai in JST Project at Kurume from 1999-2001 and has been a professor of the University of Kitakyushu since 2001. His major research interests are polysaccharides, polysaccharide/polynucleotide complexes, gene delivery, and small-angle X-ray scattering from soft materials. Based on his original nding of the polysaccharide/polynucleotide complexes, he started a bio- venture company, Napa Jen, with headquarters in California in 2005. After a major capital increase form Innovation Network Corporation of Japan (INCJ), the company name has been changed to NapaJen Pharma, Inc.
Molecular Engineering and Sciences Seminar Series
This weekly seminar brings together students, faculty and invited guests from various disciplines across campus to explore current trends in molecular engineering and nanotechnology. It is a forum for active interdisciplinary discussions. These talks are open to the public and attract a diverse audience of students and faculty.