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[摘要]：Antisense therapy, the first concept of oligonucleotide therapeutics, was proposed more than two decades ago. However, the lack of suitable delivering carriers continues to be a major obstacle to practical therapy. In this study, we present a novel complex consisting of beta-1,3-glucan and antisense oligonucleotide (AS-ODN) as a new candidate of the carriers. We used schizophyllan (SPG) as a beta-1,3-glucan and an AS-ODN sequence to suppress tumor necrosis factor alpha (TNF-alpha), where the AS-ODN has a (dA)(60) tail to induce complex with SPG. When the complexes were applied to peritoneal macrophages, they were incorporated into the cells via dectin-1 (a beta-1,3-glucan receptor expressed on antigen presenting cells) and suppressed lipopolysaccharide (LPS)-induced TNF-alpha secretion. In-vivo. AS-ODN/SPG decreased the secretion of TNF-alpha in serum and drastically reduced the inflammation of LPS-induced hepatitis. This new complex could overcome the long outstanding problem for antisense therapy because of its complexation ability, non-toxicity and high target specificity. (C) 2011 Elsevier B.V. All rights reserved. |
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