Literature DB >> 27268307

Conjugation of mono and di-GalNAc sugars enhances the potency of antisense oligonucleotides via ASGR mediated delivery to hepatocytes.

Garth A Kinberger1, Thazha P Prakash1, Jinghua Yu1, Guillermo Vasquez1, Audrey Low1, Alfred Chappell1, Karsten Schmidt1, Heather M Murray1, Hans Gaus1, Eric E Swayze1, Punit P Seth2.   

Abstract

Antisense oligonucleotides (ASOs) conjugated to trivalent GalNAc ligands show 10-fold enhanced potency for suppressing gene targets expressed in hepatocytes. Trivalent GalNAc is a high affinity ligand for the asialoglycoprotein receptor (ASGR)-a C-type lectin expressed almost exclusively on hepatocytes in the liver. In this communication, we show that conjugation of two and even one GalNAc sugar to single stranded chemically modified ASOs can enhance potency 5-10 fold in mice. Evaluation of the mono- and di-GalNAc ASO conjugates in an ASGR binding assay suggested that chemical features of the ASO enhance binding to the receptor and provide a rationale for the enhanced potency.
Copyright © 2016 Elsevier Ltd. All rights reserved.

Entities:  

Keywords:  ASGR; ASO; Delivery; GalNAc; Hepatocytes

Mesh：

Substances：

Year:  2016        PMID： 27268307     DOI： 10.1016/j.bmcl.2016.05.084

Source DB:  PubMed          Journal:  Bioorg Med Chem Lett        ISSN： 0960-894X            Impact factor:   2.823


  9 in total

Review 1.  Delivery of Oligonucleotides to the Liver with GalNAc: From Research to Registered Therapeutic Drug.

Authors:  Alexandre J Debacker; Jon Voutila; Matthew Catley; David Blakey; Nagy Habib
Journal:  Mol Ther       Date:  2020-06-17       Impact factor: 11.454

Review 2.  Selective tissue targeting of synthetic nucleic acid drugs.

Authors:  Punit P Seth; Michael Tanowitz; C Frank Bennett
Journal:  J Clin Invest       Date:  2019-01-28       Impact factor: 14.808

Review 3.  Receptor-Mediated Uptake of Phosphorothioate Antisense Oligonucleotides in Different Cell Types of the Liver.

Authors:  Colton M Miller; Michael Tanowitz; Aaron J Donner; Thazha P Prakash; Eric E Swayze; Edward N Harris; Punit P Seth
Journal:  Nucleic Acid Ther       Date:  2018-02-09       Impact factor: 5.486

Review 4.  Beyond GalNAc! Drug delivery systems comprising complex oligosaccharides for targeted use of nucleic acid therapeutics.

Authors:  Joseph O'Sullivan; Jose Muñoz-Muñoz; Graeme Turnbull; Neil Sim; Stuart Penny; Sterghios Moschos
Journal:  RSC Adv       Date:  2022-07-14       Impact factor: 4.036

5.  Characterizing the effect of GalNAc and phosphorothioate backbone on binding of antisense oligonucleotides to the asialoglycoprotein receptor.

Authors:  Karsten Schmidt; Thazha P Prakash; Aaron J Donner; Garth A Kinberger; Hans J Gaus; Audrey Low; Michael E Østergaard; Melanie Bell; Eric E Swayze; Punit P Seth
Journal:  Nucleic Acids Res       Date:  2017-03-17       Impact factor: 16.971

6.  Integrated Assessment of the Clinical Performance of GalNAc3-Conjugated 2'-O-Methoxyethyl Chimeric Antisense Oligonucleotides: I. Human Volunteer Experience.

Authors:  Stanley T Crooke; Brenda F Baker; Shuting Xia; Rosie Z Yu; Nicholas J Viney; Yanfeng Wang; Sotirios Tsimikas; Richard S Geary
Journal:  Nucleic Acid Ther       Date:  2018-12-20       Impact factor: 5.486

7.  Characterization of the interactions of chemically-modified therapeutic nucleic acids with plasma proteins using a fluorescence polarization assay.

Authors:  Hans J Gaus; Ruchi Gupta; Alfred E Chappell; Michael E Østergaard; Eric E Swayze; Punit P Seth
Journal:  Nucleic Acids Res       Date:  2019-02-20       Impact factor: 16.971

8.  Design, Synthesis and Biological Characterization of Histone Deacetylase 8 (HDAC8) Proteolysis Targeting Chimeras (PROTACs) with Anti-Neuroblastoma Activity.

Authors:  Salma Darwish; Ehab Ghazy; Tino Heimburg; Daniel Herp; Patrik Zeyen; Rabia Salem-Altintas; Johannes Ridinger; Dina Robaa; Karin Schmidtkunz; Frank Erdmann; Matthias Schmidt; Christophe Romier; Manfred Jung; Ina Oehme; Wolfgang Sippl
Journal:  Int J Mol Sci       Date:  2022-07-07       Impact factor: 6.208

Review 9.  ASGR1 and Its Enigmatic Relative, CLEC10A.

Authors:  J Kenneth Hoober
Journal:  Int J Mol Sci       Date:  2020-07-08       Impact factor: 5.923
  9 in total

北京卡尤迪生物科技股份有限公司 © 2022-2023.