In vitro selection of RNA aptamers that inhibit the activity of type A botulinum neurotoxin.
In vitro selection of RNA aptamers that inhibit the activity of type A botulinum neurotoxin.
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DOI：
10.1016/j.bbrc.2010.05.006
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发表时间：
2010-06-11
影响因子：
3.1
通讯作者：
Cai, Shuowei
中科院分区：
文献类型：
--
作者：
Chang, Tzuu-Wang;Blank, Michael;Janardhanan, Pavithra;Singh, Bal Ram;Mello, Charlene;Blind, Michael;Cai, Shuowei
A类制剂，肉毒杆菌神经毒素（BoNT），是人类已知的毒性最大的分子。BoNT轻链结构域的内肽酶活性是抑制神经递质释放和导致肉毒中毒致死性的弛缓性麻痹的原因。目前，还没有解毒剂可以逆转BoNT引起的弛缓性麻痹。在本研究中，我们通过SELEX方法鉴定了三种RNA适体，它们与A型BoNT（BoNT/A）的轻链强烈结合并抑制内肽酶活性，IC 50在低nM范围内。抑制动力学研究揭示了低nM KI和其抑制的非竞争性。适体是一类独特的治疗药物，这是首次报道其作为肉毒杆菌中毒解毒剂的发展。KI和IC 50的这些数据强烈表明，适体具有作为解毒剂的强大潜力，可以逆转BoNT/A引起的症状。
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 IC50 in low nM range. Inhibition kinetic studies reveal low nM KI 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 KI and IC50 strongly suggest that the aptamers have strong potential as antidotes that can reverse the symptom caused by BoNT/A.
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