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Development of a Monoclonal scFv against Cytotoxin to Neutralize Cytolytic Activity Induced by Naja atra Venom on Myoblast C2C12 Cells.
Toxins (Basel). 2022 07 04; 14(7)T

Abstract

The Taiwanese cobra, Naja atra, is a clinically significant species of snake observed in the wild in Taiwan. Victims bitten by N. atra usually experience severe pain and local tissue necrosis. Although antivenom is available for treatment of cobra envenomation, its neutralization potency against cobra-induced necrosis is weak, with more than 60% of cobra envenoming patients developing tissue necrosis after antivenom administration. The present study found that cytotoxin (CTX) is a key component of N. atra venom responsible for cytotoxicity against myoblast cells. Anti-CTX IgY was generated in hens, and the spleens of these hens were used to construct libraries for the development of single chain variable fragments (scFv). Two anti-CTX scFv, S1 and 2S7, were selected using phage display technology and biopanning. Both polyclonal IgY and monoclonal scFv S1 reacted specifically with CTX in cobra venom. In a cell model assay, the CTX-induced cytolytic effect was inhibited only by monoclonal scFv S1, not by polyclonal IgY. Moreover, the neutralization potency of scFv S1 was about 3.8 mg/mg, approximately three times higher than that of conventional freeze-dried neurotoxic antivenom (FNAV). Collectively, these results suggest that scFv S1 can effectively neutralize CTX-induced cytotoxicity and, when combined with currently available antivenom, can improve the potency of the latter, thereby preventing tissue damage induced by cobra envenoming.

Authors+Show Affiliations

Molecular Medicine Research Center, Chang Gung University, Taoyuan 33302, Taiwan.Department of Emergency Medicine, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan 33305, Taiwan.Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan.Department of Emergency Medicine, Yeezen General Hospital, Taoyuan 32645, Taiwan.Molecular Medicine Research Center, Chang Gung University, Taoyuan 33302, Taiwan. Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan. Liver Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan 33305, Taiwan.Molecular Medicine Research Center, Chang Gung University, Taoyuan 33302, Taiwan. Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan. Liver Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan 33305, Taiwan.School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 11042, Taiwan. Ph.D. Program in Medical Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 11042, Taiwan.Molecular Medicine Research Center, Chang Gung University, Taoyuan 33302, Taiwan.Department of Emergency Medicine, En Chu Kong Hospital, New Taipei City 23741, Taiwan.Department of Emergency Medicine, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan 33305, Taiwan.Molecular Medicine Research Center, Chang Gung University, Taoyuan 33302, Taiwan. Liver Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan 33305, Taiwan. Research Center for Food and Cosmetic Safety, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 33302, Taiwan. Department of Otolaryngology Head and Neck Surgery, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

35878197

Citation

Liu, Chien-Chun, et al. "Development of a Monoclonal scFv Against Cytotoxin to Neutralize Cytolytic Activity Induced By Naja Atra Venom On Myoblast C2C12 Cells." Toxins, vol. 14, no. 7, 2022.
Liu CC, Wu CJ, Chou TY, et al. Development of a Monoclonal scFv against Cytotoxin to Neutralize Cytolytic Activity Induced by Naja atra Venom on Myoblast C2C12 Cells. Toxins (Basel). 2022;14(7).
Liu, C. C., Wu, C. J., Chou, T. Y., Liaw, G. W., Hsiao, Y. C., Chu, L. J., Lee, C. H., Wang, P. J., Hsieh, C. H., Chen, C. K., & Yu, J. S. (2022). Development of a Monoclonal scFv against Cytotoxin to Neutralize Cytolytic Activity Induced by Naja atra Venom on Myoblast C2C12 Cells. Toxins, 14(7). https://doi.org/10.3390/toxins14070459
Liu CC, et al. Development of a Monoclonal scFv Against Cytotoxin to Neutralize Cytolytic Activity Induced By Naja Atra Venom On Myoblast C2C12 Cells. Toxins (Basel). 2022 07 4;14(7) PubMed PMID: 35878197.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Development of a Monoclonal scFv against Cytotoxin to Neutralize Cytolytic Activity Induced by Naja atra Venom on Myoblast C2C12 Cells. AU - Liu,Chien-Chun, AU - Wu,Cho-Ju, AU - Chou,Tsai-Ying, AU - Liaw,Geng-Wang, AU - Hsiao,Yung-Chin, AU - Chu,Lichieh-Julie, AU - Lee,Chi-Hsin, AU - Wang,Po-Jung, AU - Hsieh,Cheng-Hsien, AU - Chen,Chun-Kuei, AU - Yu,Jau-Song, Y1 - 2022/07/04/ PY - 2022/06/08/received PY - 2022/06/30/revised PY - 2022/06/30/accepted PY - 2022/7/25/entrez PY - 2022/7/26/pubmed PY - 2022/7/28/medline KW - Naja atra KW - cobra venom KW - cytotoxicity KW - cytotoxin (CTX) KW - necrosis KW - single-chain variable fragment (scFv) JF - Toxins JO - Toxins (Basel) VL - 14 IS - 7 N2 - The Taiwanese cobra, Naja atra, is a clinically significant species of snake observed in the wild in Taiwan. Victims bitten by N. atra usually experience severe pain and local tissue necrosis. Although antivenom is available for treatment of cobra envenomation, its neutralization potency against cobra-induced necrosis is weak, with more than 60% of cobra envenoming patients developing tissue necrosis after antivenom administration. The present study found that cytotoxin (CTX) is a key component of N. atra venom responsible for cytotoxicity against myoblast cells. Anti-CTX IgY was generated in hens, and the spleens of these hens were used to construct libraries for the development of single chain variable fragments (scFv). Two anti-CTX scFv, S1 and 2S7, were selected using phage display technology and biopanning. Both polyclonal IgY and monoclonal scFv S1 reacted specifically with CTX in cobra venom. In a cell model assay, the CTX-induced cytolytic effect was inhibited only by monoclonal scFv S1, not by polyclonal IgY. Moreover, the neutralization potency of scFv S1 was about 3.8 mg/mg, approximately three times higher than that of conventional freeze-dried neurotoxic antivenom (FNAV). Collectively, these results suggest that scFv S1 can effectively neutralize CTX-induced cytotoxicity and, when combined with currently available antivenom, can improve the potency of the latter, thereby preventing tissue damage induced by cobra envenoming. SN - 2072-6651 UR - https://www.unboundmedicine.com/medline/citation/35878197/Development_of_a_Monoclonal_scFv_against_Cytotoxin_to_Neutralize_Cytolytic_Activity_Induced_by_Naja_atra_Venom_on_Myoblast_C2C12_Cells_ L2 - https://www.mdpi.com/resolver?pii=toxins14070459 DB - PRIME DP - Unbound Medicine ER -