Literature DB >> 34141070

Site-specific Incorporation of 2',5'-Linked Nucleic Acids Enhances Therapeutic Profile of Antisense Oligonucleotides.

Thazha P Prakash1, Jinghua Yu1, Wen Shen1, Cheryl Li De Hoyos1, Andres Berdeja1, Hans Gaus1, Xue-Hai Liang1, Stanley T Crooke1, Punit P Seth1.   

Abstract

Site-specific incorporation of 2'-modifications and neutral linkages in the deoxynucleotide gap region of toxic phosphorothioate (PS) gapmer ASOs can enhance therapeutic index and safety. In this manuscript, we determined the effect of introducing 2',5'-linked RNA in the deoxynucleotide gap region on toxicity and potency of PS ASOs. Our results demonstrate that incorporation of 2',5'-linked RNA in the gap region dramatically improved hepatotoxicity profile of PS-ASOs without compromising potency and provide a novel alternate chemical approach for improving therapeutic index of ASO drugs.
© 2021 American Chemical Society.

Entities:  

Year:  2021        PMID： 34141070      PMCID： PMC8201499          DOI： 10.1021/acsmedchemlett.1c00072

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN： 1948-5875            Impact factor:   4.632


  17 in total

1.  Synthesis, biophysical properties and biological activity of second generation antisense oligonucleotides containing chiral phosphorothioate linkages.

Authors:  W Brad Wan; Michael T Migawa; Guillermo Vasquez; Heather M Murray; Josh G Nichols; Hans Gaus; Andres Berdeja; Sam Lee; Christopher E Hart; Walt F Lima; Eric E Swayze; Punit P Seth
Journal:  Nucleic Acids Res       Date:  2014-11-14       Impact factor: 16.971

2.  Physicochemical and biochemical properties of 2',5'-linked RNA and 2',5'-RNA:3',5'-RNA "hybrid" duplexes.

Authors:  M Wasner; D Arion; G Borkow; A Noronha; A H Uddin; M A Parniak; M J Damha
Journal:  Biochemistry       Date:  1998-05-19       Impact factor: 3.162

3.  Single-stranded siRNAs activate RNAi in animals.

Authors:  Walt F Lima; Thazha P Prakash; Heather M Murray; Garth A Kinberger; Wenyu Li; Alfred E Chappell; Cheryl S Li; Susan F Murray; Hans Gaus; Punit P Seth; Eric E Swayze; Stanley T Crooke
Journal:  Cell       Date:  2012-08-31       Impact factor: 41.582

4.  Structural insights into the effects of 2'-5' linkages on the RNA duplex.

Authors:  Jia Sheng; Li Li; Aaron E Engelhart; Jianhua Gan; Jiawei Wang; Jack W Szostak
Journal:  Proc Natl Acad Sci U S A       Date:  2014-02-10       Impact factor: 11.205

5.  Chemical modification of PS-ASO therapeutics reduces cellular protein-binding and improves the therapeutic index.

Authors:  Wen Shen; Cheryl L De Hoyos; Michael T Migawa; Timothy A Vickers; Hong Sun; Audrey Low; Thomas A Bell; Meghdad Rahdar; Swagatam Mukhopadhyay; Christopher E Hart; Melanie Bell; Stan Riney; Susan F Murray; Sarah Greenlee; Rosanne M Crooke; Xue-Hai Liang; Punit P Seth; Stanley T Crooke
Journal:  Nat Biotechnol       Date:  2019-04-29       Impact factor: 54.908

6.  Nonenzymic joining of oligoadenylates on a polyuridylic acid template.

Authors:  D A Usher; A H McHale
Journal:  Science       Date:  1976-04-02       Impact factor: 47.728

7.  Chirality Dependent Potency Enhancement and Structural Impact of Glycol Nucleic Acid Modification on siRNA.

Authors:  Mark K Schlegel; Donald J Foster; Alexander V Kel'in; Ivan Zlatev; Anna Bisbe; Muthusamy Jayaraman; Jeremy G Lackey; Kallanthottathil G Rajeev; Klaus Charissé; Joel Harp; Pradeep S Pallan; Martin A Maier; Martin Egli; Muthiah Manoharan
Journal:  J Am Chem Soc       Date:  2017-06-19       Impact factor: 15.419

8.  Re-Engineering RNA Molecules into Therapeutic Agents.

Authors:  Martin Egli; Muthiah Manoharan
Journal:  Acc Chem Res       Date:  2019-03-26       Impact factor: 22.384

9.  RNA interference by 2',5'-linked nucleic acid duplexes in mammalian cells.

Authors:  Thazha P Prakash; Bryan Kraynack; Brenda F Baker; Eric E Swayze; Balkrishen Bhat
Journal:  Bioorg Med Chem Lett       Date:  2006-04-17       Impact factor: 2.823

10.  Oligoribonucleotides containing 2',5'-phosphodiester linkages exhibit binding selectivity for 3',5'-RNA over 3',5'-ssDNA.

Authors:  P A Giannaris; M J Damha
Journal:  Nucleic Acids Res       Date:  1993-10-11       Impact factor: 16.971
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  1 in total

1.  Identification of nucleobase chemical modifications that reduce the hepatotoxicity of gapmer antisense oligonucleotides.

Authors:  Tokuyuki Yoshida; Kunihiko Morihiro; Yuki Naito; Atsushi Mikami; Yuuya Kasahara; Takao Inoue; Satoshi Obika
Journal:  Nucleic Acids Res       Date:  2022-07-22       Impact factor: 19.160
  1 in total

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