{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:43:14Z","timestamp":1769906594465,"version":"3.49.0"},"reference-count":16,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2019,1,9]],"date-time":"2019-01-09T00:00:00Z","timestamp":1546992000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001674","name":"Fondation Leducq","doi-asserted-by":"publisher","award":["ERPT equipment"],"award-info":[{"award-number":["ERPT equipment"]}],"id":[{"id":"10.13039\/501100001674","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-11-LABX-0015"],"award-info":[{"award-number":["ANR-11-LABX-0015"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The medical staff is often powerless to treat patients affected by drug abuse or misuse and poisoning. In the case of envenomation, the treatment of choice remains horse sera administration that poses a wealth of other medical conditions and threats. Previously, we have demonstrated that DNA-based aptamers represent powerful neutralizing tools for lethal animal toxins of venomous origin. Herein, we further pursued our investigations in order to understand whether all toxin-interacting aptamers possessed equivalent potencies to neutralize \u03b1C-conotoxin PrXA in vitro and in vivo. We confirmed the high lethality in mice produced by \u03b1C-conotoxin PrXA regardless of the mode of injection and further characterized myoclonus produced by the toxin. We used high-throughput patch-clamp technology to assess the effect of \u03b1C-conotoxin PrXA on ACh-mediated responses in TE671 cells, responses that are carried by muscle-type nicotinic receptors. We show that 2 out of 4 aptamers reduce the affinity of the toxin for its receptor, most likely by interfering with the pharmacophore. In vivo, more complex responses on myoclonus and mice lethality are observed depending on the type of aptamer and mode of administration (concomitant or differed). Concomitant administration always works better than differed administration indicating the stability of the complex in vivo. The most remarkable conclusion is that an aptamer that has no or a limited efficacy in vitro may nevertheless be functional in vivo probably owing to an impact on the biodistribution or pharmacokinetics of the toxin in vivo. Overall, the results highlight that a blind selection of aptamers against toxins leads to efficient neutralizing compounds in vivo regardless of the mode of action. This opens the door to the use of aptamer mixtures as substitutes to horse sera for the neutralization of life-threatening animal venoms, an important WHO concern in tropical areas.<\/jats:p>","DOI":"10.3390\/molecules24020229","type":"journal-article","created":{"date-parts":[[2019,1,10]],"date-time":"2019-01-10T03:22:31Z","timestamp":1547090551000},"page":"229","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Aptamer Efficacies for In Vitro and In Vivo Modulation of \u03b1C-Conotoxin PrXA Pharmacology"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7771-0268","authenticated-orcid":false,"given":"Germain Sotoing","family":"Taiwe","sequence":"first","affiliation":[{"name":"INSERM UMR 1087\/CNRS UMR 6291, Institut du Thorax, Nouvelle Universit\u00e9 \u00e0 Nantes, LabEx Ion Channels, Science and Therapeutics, 8 Quai Moncousu, BP 70721 Nantes CEDEX 1, France"},{"name":"Department of Zoology and Animal Physiology, Faculty of Sciences, University of Buea, P.O. Box 63, Buea, Cameroon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00e9r\u00f4me","family":"Montnach","sequence":"additional","affiliation":[{"name":"INSERM UMR 1087\/CNRS UMR 6291, Institut du Thorax, Nouvelle Universit\u00e9 \u00e0 Nantes, LabEx Ion Channels, Science and Therapeutics, 8 Quai Moncousu, BP 70721 Nantes CEDEX 1, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S\u00e9bastien","family":"Nicolas","sequence":"additional","affiliation":[{"name":"INSERM UMR 1087\/CNRS UMR 6291, Institut du Thorax, Nouvelle Universit\u00e9 \u00e0 Nantes, LabEx Ion Channels, Science and Therapeutics, 8 Quai Moncousu, BP 70721 Nantes CEDEX 1, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"St\u00e9phan","family":"De Waard","sequence":"additional","affiliation":[{"name":"INSERM UMR 1087\/CNRS UMR 6291, Institut du Thorax, Nouvelle Universit\u00e9 \u00e0 Nantes, LabEx Ion Channels, Science and Therapeutics, 8 Quai Moncousu, BP 70721 Nantes CEDEX 1, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emmanuelle","family":"Fiore","sequence":"additional","affiliation":[{"name":"CNRS, DPM UMR 5063, University Grenoble Alpes, 38041 Grenoble, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5558-6369","authenticated-orcid":false,"given":"Eric","family":"Peyrin","sequence":"additional","affiliation":[{"name":"CNRS, DPM UMR 5063, University Grenoble Alpes, 38041 Grenoble, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3441-9673","authenticated-orcid":false,"given":"Tarek Mohamed Abd","family":"El-Aziz","sequence":"additional","affiliation":[{"name":"Zoology Department, Faculty of Science, Minia University, 61519 El-Minia, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muriel","family":"Amar","sequence":"additional","affiliation":[{"name":"Service d\u2019Ing\u00e9nierie Mol\u00e9culaire des Prot\u00e9ines, Institut des Sciences du Vivant Fr\u00e9d\u00e9ric Joliot, Commissariat \u00e0 l\u2019Energie Atomique, Universit\u00e9 Paris-Saclay, F-91191 Gif sur Yvette, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0693-8994","authenticated-orcid":false,"given":"Jordi","family":"Molg\u00f3","sequence":"additional","affiliation":[{"name":"Service d\u2019Ing\u00e9nierie Mol\u00e9culaire des Prot\u00e9ines, Institut des Sciences du Vivant Fr\u00e9d\u00e9ric Joliot, Commissariat \u00e0 l\u2019Energie Atomique, Universit\u00e9 Paris-Saclay, F-91191 Gif sur Yvette, France"},{"name":"Institut des Neurosciences Paris-Saclay, UMR 9197, CNRS\/Universit\u00e9 Paris-Sud, 91198 Gif sur Yvette, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel","family":"Ronjat","sequence":"additional","affiliation":[{"name":"INSERM UMR 1087\/CNRS UMR 6291, Institut du Thorax, Nouvelle Universit\u00e9 \u00e0 Nantes, LabEx Ion Channels, Science and Therapeutics, 8 Quai Moncousu, BP 70721 Nantes CEDEX 1, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denis","family":"Servent","sequence":"additional","affiliation":[{"name":"Service d\u2019Ing\u00e9nierie Mol\u00e9culaire des Prot\u00e9ines, Institut des Sciences du Vivant Fr\u00e9d\u00e9ric Joliot, Commissariat \u00e0 l\u2019Energie Atomique, Universit\u00e9 Paris-Saclay, F-91191 Gif sur Yvette, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corinne","family":"Ravelet","sequence":"additional","affiliation":[{"name":"CNRS, DPM UMR 5063, University Grenoble Alpes, 38041 Grenoble, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2782-9615","authenticated-orcid":false,"given":"Michel","family":"De Waard","sequence":"additional","affiliation":[{"name":"INSERM UMR 1087\/CNRS UMR 6291, Institut du Thorax, Nouvelle Universit\u00e9 \u00e0 Nantes, LabEx Ion Channels, Science and Therapeutics, 8 Quai Moncousu, BP 70721 Nantes CEDEX 1, France"},{"name":"Smartox Biotechnology, 6 rue des Platanes, 38120 Saint Egr\u00e8ve, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,1,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/0041-0101(94)90087-6","article-title":"Caprylic acid fractionation of hyperimmune horse plasma: Description of a simple procedure for antivenom production","volume":"32","author":"Rojas","year":"1994","journal-title":"Toxicon"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1016\/S0041-0101(99)00086-0","article-title":"Doctor Albert Calmette 1863\u20131933: Founder of antivenomous serotherapy and of antituberculous BCG vaccination","volume":"37","author":"Hawgood","year":"1999","journal-title":"Toxicon"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1126\/science.343.6166.16","article-title":"Drug industry. For Mexican antivenom maker, U.S. market is a snake pit","volume":"343","author":"Wade","year":"2014","journal-title":"Science"},{"key":"ref_4","first-page":"129","article-title":"Antivenoms for the treatment of snakebite envenomings: The road ahead","volume":"39","author":"Gutierrez","year":"2011","journal-title":"Biol. J. Int. Assoc. Biol. Stand."},{"key":"ref_5","unstructured":"WHO (2010). WHO Guidelines for the Production, Control and Regulation of Snake Antivenom Immunoglobulins, World Health Organization."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"517","DOI":"10.4161\/mabs.3.6.17621","article-title":"Antibodies for biodefense","volume":"3","author":"Froude","year":"2011","journal-title":"mAbs"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.cell.2010.01.043","article-title":"Inhibition of retrograde transport protects mice from lethal ricin challenge","volume":"141","author":"Stechmann","year":"2010","journal-title":"Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"7202","DOI":"10.1038\/s41598-017-07554-5","article-title":"Efficient functional neutralization of lethal peptide toxins in vivo by oligonucleotides","volume":"7","author":"Ravelet","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4937","DOI":"10.1074\/jbc.275.7.4937","article-title":"In vitro selection of RNA molecules that inhibit the activity of ricin A-chain","volume":"275","author":"Hesselberth","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1124\/pr.111.005322","article-title":"Conus venom peptide pharmacology","volume":"64","author":"Lewis","year":"2012","journal-title":"Pharmacol. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"8717","DOI":"10.1021\/bi700582m","article-title":"AlphaC-conotoxin PrXA: A new family of nicotinic acetylcholine receptor antagonists","volume":"46","author":"Jimenez","year":"2007","journal-title":"Biochemistry"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1093\/carcin\/10.5.899","article-title":"Characterization of the human cell line TE671","volume":"10","author":"Stratton","year":"1989","journal-title":"Carcinogenesis"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/0014-5793(88)81430-3","article-title":"The human medulloblastoma cell line TE671 expresses a muscle-like acetylcholine receptor. Cloning of the alpha-subunit cDNA","volume":"226","author":"Schoepfer","year":"1988","journal-title":"FEBS Lett."},{"key":"ref_14","first-page":"1269","article-title":"Potentiation and inhibition of nicotinic acetylcholine receptors by spermine in the TE671 human muscle cell line","volume":"286","author":"Shao","year":"1998","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3406","DOI":"10.1093\/nar\/gkg595","article-title":"Mfold web server for nucleic acid folding and hybridization prediction","volume":"31","author":"Zuker","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3520","DOI":"10.1039\/c2an35159e","article-title":"Surface functionalization chemistries on highly sensitive silica-based sensor chips","volume":"137","author":"Gopinath","year":"2012","journal-title":"Analyst"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/2\/229\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:24:44Z","timestamp":1760185484000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/2\/229"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,9]]},"references-count":16,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2019,1]]}},"alternative-id":["molecules24020229"],"URL":"https:\/\/doi.org\/10.3390\/molecules24020229","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,9]]}}}