Open AccessEfficient functional neutralization of lethal peptide toxins in vivo by oligonucleotides
Author(s) -
Tarek Mohamed Abd El-Aziz,
Corinne Ravelet,
Jordi Molgó,
Emmanuelle Fiore,
Simon Palé,
Muriel Amar,
Sawsan Al-Khoury,
Jérôme Dejeu,
Mahmoud Fadl,
Michel Ronjat,
Germain Sotoing Taïwe,
Denis Servent,
Eric Peyrin,
Michel De Waard
Publication year - 2017
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/s41598-017-07554-5
Subject(s) - aptamer , in vivo , neutralization , pharmacophore , venom , conotoxin , peptide , pharmacology , oligonucleotide , envenomation , biology , chemistry , computational biology , virology , dna , biochemistry , microbiology and biotechnology , virus , genetics
Medical means to save the life of human patients affected by drug abuse, envenomation or critical poisoning are currently limited. While the compounds at risks are most often well identified, particularly for bioterrorism, chemical intervention to counteract the toxic effects of the ingested/injected compound(s) is restricted to the use of antibodies. Herein, we illustrate that DNA aptamers, targeted to block the pharmacophore of a poisonous compound, represent a fast-acting and reliable method of neutralization in vivo that possesses efficient and long-lasting life-saving properties. For this proof of concept, we used one putative bioweapon, αC-conotoxin PrXA, a marine snail ultrafast-killing paralytic toxin, to identify peptide-binding DNA aptamers. We illustrate that they can efficiently neutralize the toxin-induced (i) displacement of [ 125 I]-α-bungarotoxin binding onto nicotinic receptors, (ii) inhibition of diaphragm muscle contraction, and (iii) lethality in mice. Our results demonstrate the preclinical value of DNA aptamers as fast-acting, safe and cheap antidotes to lethal toxins at risk of misuse in bioterrorism and offer hope for an alternative method than donor sera to treat cases of envenomation.