title: 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.affiliation: Department of Chemistry and Biochemistry, and Botulinum Research Center, University of Massachusetts Dartmouth, North Dartmouth, MA 02747, USA.
authors.forename: Tzuu-Wang
authors.initials: TW
authors.lastname: Chang
authors.forename: Michael
authors.initials: M
authors.lastname: Blank
authors.forename: Pavithra
authors.initials: P
authors.lastname: Janardhanan
authors.forename: Bal Ram
authors.initials: BR
authors.lastname: Singh
authors.forename: Charlene
authors.initials: C
authors.lastname: Mello
authors.forename: Michael
authors.initials: M
authors.lastname: Blind
authors.forename: Shuowei
authors.initials: S
authors.lastname: Cai
mesh_terms: D000931:Antidotes / Q000737:chemistry* / Q000494:pharmacology; D052157:Aptamers, Nucleotide / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D001483:Base Sequence; D019274:Botulinum Toxins, Type A / Q000037:antagonists & inhibitors*; D052156:SELEX Aptamer Technique
chemical_list: D000931:Antidotes; D052157:Aptamers, Nucleotide; D019274:Botulinum Toxins, Type A
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