Galactose-PEG dual conjugation of β-(1→3)-D-glucan schizophyllan for antisense oligonucleotides delivery to enhance the cellular uptake

Ryouji Karinaga, Takahisa Anada, Jusaku Minari, Masami Mizu, Kazuya Koumoto, Junji Fukuda, Kohji Nakazawa, Teruaki Hasegawa, Munenori Numata, Seiji Shinkai, Kazuo Sakurai

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25 Citations (Scopus)

Abstract

Antisense oligonucleotides (AS ODNs) are applied to silence a particular gene, and this approach is one of the potential gene therapies. However, naked oligonucleotides are easy to be degraded or absorbed in biological condition. Therefore, we need a carrier to deliver AS ODNs. This paper presents galactose moieties that were conjugated to the side chain of SPG to enhance cellular ingestion through endocytosis mediated by asialoglycoprotein receptor specifically located on parenchymal liver cells. We introduced galactose with two types of chemical bonds; amide and amine, and the amine connection showed lower ingestion and more toxicity than the amide one. Since PEG was known to induce endocytosis escape, we combined PEG and galactose aiming to provide both cellular up-take and subsequent endocytosis escape. We designed lactose or galactose moieties to attach to the end of the PEG chain that connects to the SPG side chain. When the PEG had the molecular weight of 5000-6000, the antisense effect reached the maximum. We believe that this new type of galactose and PEG dual conjugation broaden the horizon in antisense delivery.

Original languageEnglish
Pages (from-to)1626-1635
Number of pages10
JournalBiomaterials
Volume27
Issue number8
DOIs
Publication statusPublished - Mar 1 2006

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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    Karinaga, R., Anada, T., Minari, J., Mizu, M., Koumoto, K., Fukuda, J., Nakazawa, K., Hasegawa, T., Numata, M., Shinkai, S., & Sakurai, K. (2006). Galactose-PEG dual conjugation of β-(1→3)-D-glucan schizophyllan for antisense oligonucleotides delivery to enhance the cellular uptake. Biomaterials, 27(8), 1626-1635. https://doi.org/10.1016/j.biomaterials.2005.08.023