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Programmed Instability of Ligand Conjugation Manifold for Efficient Hepatocyte Delivery of Therapeutic Oligonucleotides by Chisato Terada; Fumito Wada; Mei Uchida; Yukari Yasutomi; Kaho Oh; Seiya Kawamoto; Yukina Kayaba; Asako Yamayoshi; Mariko Harada-Shiba; Satoshi Obika; Tsuyoshi Yamamoto is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.
What is Programmed Instability of Ligand Conjugation Manifold for Efficient Hepatocyte Delivery of Therapeutic Oligonucleotides about?
Ligand-targeted drug delivery (LTDD) has gained more attention in the field of nucleic acid therapeutics. To further elicit the potential of therapeutic oligonucleotides by means of LTDD, we newly developed ()- and ()-3-amino-1,2-propanediol (APD) manifold for ligand conjugation. -acetylgalactosamine (GalNAc)/asialoglycoprotein receptor (ASGPr) system has been shown to be a powerful and robust paradigm of LTDD. Our novel APD-based GalNAc (GalNAc) was shown to have intrinsic chemical instability that could play a role in better manipulation of active drug release. The APD manifold also enables facile production of conjugates through an on-support ligand cluster synthesis. We showed in a series of studies that while the knockdown activity of antisense oligonucleotides (ASOs) bearing 5'-GalNAc was comparable to the conventional hydroxy-L-prolinol-linked GalNAc (GalNAc), 3'-GalNAc elicited ASO activity by more than twice as much as the conventional 3'-GalNAc. This was ascribed partly to the GalNAc's ideal susceptibility to nucleolytic digestion, which is expected to facilitate cytosolic internalization of ASO drugs. Moreover, an / imaging study visualized the enhancement effect of mono
Who reads Programmed Instability of Ligand Conjugation Manifold for Efficient Hepatocyte Delivery of Therapeutic Oligonucleotides?
It is typically read by researchers, students, and practitioners in Biochemistry, Genetics and Molecular Biology.
- Author
- Chisato Terada; Fumito Wada; Mei Uchida; Yukari Yasutomi; Kaho Oh; Seiya Kawamoto; Yukina Kayaba; Asako Yamayoshi; Mariko Harada-Shiba; Satoshi Obika; Tsuyoshi Yamamoto
- Published
- 2021
- Language
- EN
- Field
- Biochemistry, Genetics and Molecular Biology (Life Sciences)