In vitro selection of RNA aptamers that inhibit the activity of type A botulinum neurotoxin.

Abstract

The category A agent, botulinum neurotoxin (BoNT), is the most toxic molecule known to mankind. The endopeptidase activity of light chain domain of BoNT is the cause for the inhibition of the neurotransmitter release and the flaccid paralysis that leads to lethality in botulism. Currently, antidotes are not available to reverse the flaccid paralysis caused by BoNT. In the present study, we have identified three RNA aptamers through SELEX-process, which bind strongly to the light chain of type A BoNT (BoNT/A) and inhibit the endopeptidase activity, with IC(50) in low nM range. Inhibition kinetic studies reveal low nM K(I) and non-competitive nature of their inhibition. Aptamers are unique group of molecules as therapeutics, and this is first report of their development as an antidote against botulism. These data on K(I) and IC(50) strongly suggest that the aptamers have strong potential as antidotes that can reverse the symptom caused by BoNT/A.

• Authors: Tzuu-Wang Chang, Michael Blank, Pavithra Janardhanan, Bal Ram Singh, Charlene Mello, Michael Blind, Shuowei Cai
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 396 Issue 4 Pg. 854-60 (Jun 11 2010) ISSN: 1090-2104 [Electronic] United States
• PMID: 20452328 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: (c) 2010 Elsevier Inc. All rights reserved.

Chemical References

• Antidotes
• Aptamers, Nucleotide
• Botulinum Toxins, Type A

Topics

• Antidotes (chemistry, pharmacology)
• Aptamers, Nucleotide (chemistry, isolation & purification, pharmacology)
• Base Sequence
• Botulinum Toxins, Type A (antagonists & inhibitors)
• SELEX Aptamer Technique