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...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2017-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-07554-5 |
| _version_ | 1818421908901724160 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T13:17:50Z |
| format | Article |
| id | doaj.art-b6e08015bd244b748e280b5f39b01721 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-14T13:17:50Z |
| publishDate | 2017-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-b6e08015bd244b748e280b5f39b017212022-12-21T23:00:00ZengNature PortfolioScientific Reports2045-23222017-08-01711910.1038/s41598-017-07554-5Efficient functional neutralization of lethal peptide toxins in vivo by oligonucleotidesTarek Mohamed Abd El-Aziz0Corinne Ravelet1Jordi Molgo2Emmanuelle Fiore3Simon Pale4Muriel Amar5Sawsan Al-Khoury6Jérôme Dejeu7Mahmoud Fadl8Michel Ronjat9Germain Sotoing Taiwe10Denis Servent11Eric Peyrin12Michel De Waard13INSERM UMR 1087/CNRS UMR 6291, Institute of Thorax, LabEx Ion Channels, Science and Therapeutics, 8 Quai Moncousu, BP 70721University Grenoble AlpesService d’Ingénierie Moléculaire des Protéines (SIMOPRO), IBITECS, Commissariat à l’Energie Atomique, Université Paris-SaclayUniversity Grenoble AlpesDepartment of Zoology and Animal Physiology, Faculty of Sciences, University of Buea, P. O. Box 63Service d’Ingénierie Moléculaire des Protéines (SIMOPRO), IBITECS, Commissariat à l’Energie Atomique, Université Paris-SaclayINSERM UMR 1087/CNRS UMR 6291, Institute of Thorax, LabEx Ion Channels, Science and Therapeutics, 8 Quai Moncousu, BP 70721University Grenoble AlpesZoology Department, Faculty of Science, Minia UniversityINSERM UMR 1087/CNRS UMR 6291, Institute of Thorax, LabEx Ion Channels, Science and Therapeutics, 8 Quai Moncousu, BP 70721CNRS, DCM UMR 5250, Bâtiment Nanobio, BP 53Service d’Ingénierie Moléculaire des Protéines (SIMOPRO), IBITECS, Commissariat à l’Energie Atomique, Université Paris-SaclayUniversity Grenoble AlpesINSERM UMR 1087/CNRS UMR 6291, Institute of Thorax, LabEx Ion Channels, Science and Therapeutics, 8 Quai Moncousu, BP 70721Abstract 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.https://doi.org/10.1038/s41598-017-07554-5 |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | Efficient functional neutralization of lethal peptide toxins in vivo by oligonucleotides |
| title_sort | efficient functional neutralization of lethal peptide toxins in vivo by oligonucleotides |
| url | https://doi.org/10.1038/s41598-017-07554-5 |
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