Efficient functional neutralization of lethal peptide toxins in vivo by oligonucleotides
Abstract 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 ingeste...
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Nature Portfolio
2017
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oai:doaj.org-article:b6e08015bd244b748e280b5f39b017212021-12-02T11:52:22ZEfficient functional neutralization of lethal peptide toxins in vivo by oligonucleotides10.1038/s41598-017-07554-52045-2322https://doaj.org/article/b6e08015bd244b748e280b5f39b017212017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07554-5https://doaj.org/toc/2045-2322Abstract 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 [125I]-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.Tarek Mohamed Abd El-AzizCorinne RaveletJordi MolgoEmmanuelle FioreSimon PaleMuriel AmarSawsan Al-KhouryJérôme DejeuMahmoud FadlMichel RonjatGermain Sotoing TaiweDenis ServentEric PeyrinMichel De WaardNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017) |
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Medicine R Science Q Tarek Mohamed Abd El-Aziz Corinne Ravelet Jordi Molgo Emmanuelle Fiore Simon Pale Muriel Amar Sawsan Al-Khoury Jérôme Dejeu Mahmoud Fadl Michel Ronjat Germain Sotoing Taiwe Denis Servent Eric Peyrin Michel De Waard Efficient functional neutralization of lethal peptide toxins in vivo by oligonucleotides |
| description |
Abstract 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 [125I]-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. |
| format |
article |
| author |
Tarek Mohamed Abd El-Aziz Corinne Ravelet Jordi Molgo Emmanuelle Fiore Simon Pale Muriel Amar Sawsan Al-Khoury Jérôme Dejeu Mahmoud Fadl Michel Ronjat Germain Sotoing Taiwe Denis Servent Eric Peyrin Michel De Waard |
| author_facet |
Tarek Mohamed Abd El-Aziz Corinne Ravelet Jordi Molgo Emmanuelle Fiore Simon Pale Muriel Amar Sawsan Al-Khoury Jérôme Dejeu Mahmoud Fadl Michel Ronjat Germain Sotoing Taiwe Denis Servent Eric Peyrin Michel De Waard |
| author_sort |
Tarek Mohamed Abd El-Aziz |
| title |
Efficient functional neutralization of lethal peptide toxins in vivo by oligonucleotides |
| title_short |
Efficient functional neutralization of lethal peptide toxins in vivo by oligonucleotides |
| title_full |
Efficient functional neutralization of lethal peptide toxins in vivo by oligonucleotides |
| title_fullStr |
Efficient functional neutralization of lethal peptide toxins in vivo by oligonucleotides |
| title_full_unstemmed |
Efficient functional neutralization of lethal peptide toxins in vivo by oligonucleotides |
| title_sort |
efficient functional neutralization of lethal peptide toxins in vivo by oligonucleotides |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/b6e08015bd244b748e280b5f39b01721 |
| work_keys_str_mv |
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