Gene silencing using a conjugate comprising Tat peptide and antisense oligonucleotide with phosphorothioate backbones

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• 作者：Yoshiya Maegawa^a ; Shinichi Mochizuki^a ; ^{mochizuki@kitakyu-u.ac.jp" class="auth_mail" title="E-mail the corresponding author} ; Noriko Miyamoto^a ; Kazuo Sakurai^a ; ^b ; ^{sakurai@kitakyu-u.ac.jp" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Antisense oligonucleotide ; Tat peptide ; Conjugate ; Click Chemistry
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：15 February 2016
• 年：2016
• 卷：26
• 期：4
• 页码：1276-1278
• 全文大小：462 K

文摘

Antisense oligonucleotides (ASOs) have a great therapeutic potential for the modulation of gene expression because of the high specificity. The major obstacles for clinical application are enzymatic degradation and low uptake into cells in vivo. In this study, we prepared the conjugate comprising Tat peptide and ASO with phosphorothioate linkages in a simple manner; azide alkyne Huisgen cycloaddition using a copper catalyst. The obtained conjugate showed a high stability in serum, compared with the conjugate with phosphodiester linkages. The conjugates with antisense for c-myb that is transcriptional factor concerning cell growth inhibited the cell proliferation in a dose dependent manner sequence-specifically. These findings suggest Tat-mediated ASOs delivery is useful for the treatment of various diseases.