Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred

12 Issues per year


IMPACT FACTOR 2016: 3.273

CiteScore 2016: 3.01

SCImago Journal Rank (SJR) 2016: 1.679
Source Normalized Impact per Paper (SNIP) 2016: 0.800

Online
ISSN
1437-4315
See all formats and pricing
More options …
Volume 392, Issue 4

Issues

Allele-selective inhibition of ataxin-3 (ATX3) expression by antisense oligomers and duplex RNAs

Jiaxin Hu
  • Departments of Pharmacology and Biochemistry, UT Southwestern Medical Center, Dallas, TX 75390-9041, USA
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Keith T. Gagnon
  • Departments of Pharmacology and Biochemistry, UT Southwestern Medical Center, Dallas, TX 75390-9041, USA
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Jing Liu
  • Departments of Pharmacology and Biochemistry, UT Southwestern Medical Center, Dallas, TX 75390-9041, USA
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Jonathan K. Watts
  • Departments of Pharmacology and Biochemistry, UT Southwestern Medical Center, Dallas, TX 75390-9041, USA
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Jeja Syeda-Nawaz
  • Departments of Pharmacology and Biochemistry, UT Southwestern Medical Center, Dallas, TX 75390-9041, USA
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ C. Frank Bennett / Eric E. Swayze / John Randolph / Jyoti Chattopadhyaya
  • Department of Bioorganic Chemistry, Uppsala University, Biomedical Center, Box 581, S-751 23 Uppsala, Sweden
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ David R. Corey
Published Online: 2011-07-25 | DOI: https://doi.org/10.1515/bc.2011.045

Abstract

Spinocerebellar ataxia-3 (also known as Machado-Joseph disease) is an incurable neurodegenerative disorder caused by expression of a mutant variant of ataxin-3 (ATX3) protein. Inhibiting expression of ATX3 would provide a therapeutic strategy, but indiscriminant inhibition of both wild-type and mutant ATX3 might lead to undesirable side effects. An ideal silencing agent would block expression of mutant ATX3 while leaving expression of wild-type ATX3 intact. We have previously observed that peptide nucleic acid (PNA) conjugates targeting the expanded CAG repeat within ATX3 mRNA block expression of both alleles. We have now identified additional PNAs capable of inhibiting ATX3 expression that vary in length and in the nature of the conjugated cation chain. We can also achieve potent and selective inhibition using duplex RNAs containing one or more mismatches relative to the CAG repeat. Anti-CAG antisense bridged nucleic acid oligonucleotides that lack a cationic domain are potent inhibitors but are not allele-selective. Allele-selective inhibitors of ATX3 expression provide insights into the mechanism of selectivity and promising lead compounds for further development and in vivo investigation.

Keywords: allele-selective; ataxin-3; peptide nucleic acid; siRNA; spinocerebellar ataxia-3

About the article

Corresponding author


Received: 2010-11-17

Accepted: 2011-01-07

Published Online: 2011-07-25

Published in Print: 2011-04-01


Citation Information: Biological Chemistry, Volume 392, Issue 4, Pages 315–325, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/bc.2011.045.

Export Citation

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

[1]
Lauren R. Moore, Gautam Rajpal, Ian T. Dillingham, Maya Qutob, Kate G. Blumenstein, Danielle Gattis, Gene Hung, Holly B. Kordasiewicz, Henry L. Paulson, and Hayley S. McLoughlin
Molecular Therapy - Nucleic Acids, 2017, Volume 7, Page 200
[2]
Agnieszka Fiszer, Joanna Wroblewska, Bartosz Nowak, and Wlodzimierz Krzyzosiak
Genes, 2016, Volume 7, Number 12, Page 132
[3]
Fengzhen Huang, Li Zhang, Zhe Long, Zhao Chen, Xuan Hou, Chunrong Wang, Huirong Peng, Junling Wang, Jiada Li, Ranhui Duan, Kun Xia, De-Maw Chuang, Beisha Tang, and Hong Jiang
FEBS Letters, 2014, Volume 588, Number 24, Page 4791
[4]
Agnieszka Kiliszek and Wojciech Rypniewski
Nucleic Acids Research, 2014, Volume 42, Number 13, Page 8189
[5]
A. Fiszer and W. J. Krzyzosiak
Nucleic Acids Research, 2014, Volume 42, Number 11, Page 6787
[6]
Agnieszka Fiszer, Marta Olejniczak, Paulina Galka-Marciniak, Agnieszka Mykowska, and Wlodzimierz J. Krzyzosiak
Nucleic Acids Research, 2013, Volume 41, Number 22, Page 10426
[7]
Jing Liu, Dongbo Yu, Yuichiro Aiba, Hannah Pendergraff, Eric E. Swayze, Walt F. Lima, Jiaxin Hu, Thazha P. Prakash, and David R. Corey
Nucleic Acids Research, 2013, Volume 41, Number 20, Page 9570
[8]
J. Liu, H. Pendergraff, K. J. Narayanannair, J. G. Lackey, S. Kuchimanchi, K. G. Rajeev, M. Manoharan, J. Hu, and D. R. Corey
Nucleic Acids Research, 2013, Volume 41, Number 18, Page 8788
[9]
Melvin M. Evers, Hoang-Dai Tran, Ioannis Zalachoras, Barry A. Pepers, Onno C. Meijer, Johan T. den Dunnen, Gert-Jan B. van Ommen, Annemieke Aartsma-Rus, and Willeke M.C. van Roon-Mom
Neurobiology of Disease, 2013, Volume 58, Page 49
[10]
Olga Khorkova, Jane Hsiao, and Claes Wahlestedt
Pharmaceutical Patent Analyst, 2013, Volume 2, Number 2, Page 215
[11]
Jiaxin Hu, Jing Liu, Dongbo Yu, Yongjun Chu, and David R. Corey
Nucleic Acids Research, 2012, Volume 40, Number 22, Page 11270
[12]
Amber L. Southwell, Niels H. Skotte, C. Frank Bennett, and Michael R. Hayden
Trends in Molecular Medicine, 2012, Volume 18, Number 11, Page 634
[13]
Dongbo Yu, Hannah Pendergraff, Jing Liu, Holly B. Kordasiewicz, Don W. Cleveland, Eric E. Swayze, Walt F. Lima, Stanley T. Crooke, Thazha P. Prakash, and David R. Corey
Cell, 2012, Volume 150, Number 5, Page 895
[15]
Masayuki Matsui and David R. Corey
Drug Discovery Today, 2012, Volume 17, Number 9-10, Page 443
[16]
W. J. Krzyzosiak, K. Sobczak, M. Wojciechowska, A. Fiszer, A. Mykowska, and P. Kozlowski
Nucleic Acids Research, 2012, Volume 40, Number 1, Page 11
[17]
Maria do Carmo Costa and Henry L. Paulson
Progress in Neurobiology, 2012, Volume 97, Number 2, Page 239
[18]
Dagmar Klostermeier
Biological Chemistry, 2011, Volume 392, Number 4

Comments (0)

Please log in or register to comment.
Log in