Dear Editor,Small conductance Ca2＋-activated potassium （SK） channels are widely expressed in various tissues and play a unique role in regulating cell function by integrating cytosolic Ca2＋ levels and membrane pot...Dear Editor,Small conductance Ca2＋-activated potassium （SK） channels are widely expressed in various tissues and play a unique role in regulating cell function by integrating cytosolic Ca2＋ levels and membrane potential （Adelman et al., 2012）. Xu et al. first identified SK channels in the heart and found that SK channels, particularly the SK2 channel, are preferentially expressed in human and mouse atrial myocytes but not in ventricular myocytes （Xu et al., 2003）. This suggests that the SK展开更多
Given their dangerous effects on the nervous system,neurotoxins represent a significant threat to public health.Various therapeutic approaches,including chelating agents,receptor decoys,and toxin-neutralizing antibodi...Given their dangerous effects on the nervous system,neurotoxins represent a significant threat to public health.Various therapeutic approaches,including chelating agents,receptor decoys,and toxin-neutralizing antibodies,have been explored.While prophylactic vaccines are desirable,it is oftentimes difficult to effectively balance their safety and efficacy given the highly dangerous nature of neurotoxins.To address this,we report here on a nanovaccine against neurotoxins that leverages the detoxifying properties of cell membrane-coated nanoparticles.A genetically modified cell line with constitutive overexpression of theα7 nicotinic acetylcholine receptor is developed as a membrane source to generate biomimetic nanoparticles that can effectively and irreversibly bind toα-bungarotoxin,a model neurotoxin.This abrogates the biological activity of the toxin,enabling the resulting nanotoxoid to be safely delivered into the body and processed by the immune system.When co-administered with an immunological adjuvant,a strong humoral response againstα-bungarotoxin is generated that protects vaccinated mice against a lethal dose of the toxin.Overall,this work highlights the potential of using genetic modification strategies to develop nanotoxoid formulations against various biological threats.展开更多
基金supported by the National Natural Science Foundation of China (30870903 to Xiaorong Zeng, 31300948,81670130 to Xiaoqiu Tan, 81670313 to Jimin Cao)Science and Technology Support Program of Sichuan Province (2011FZ0106 to Xiaorong Zeng)
文摘Dear Editor,Small conductance Ca2＋-activated potassium （SK） channels are widely expressed in various tissues and play a unique role in regulating cell function by integrating cytosolic Ca2＋ levels and membrane potential （Adelman et al., 2012）. Xu et al. first identified SK channels in the heart and found that SK channels, particularly the SK2 channel, are preferentially expressed in human and mouse atrial myocytes but not in ventricular myocytes （Xu et al., 2003）. This suggests that the SK
基金supported by the Defense Threat Reduction Agency Joint Science and Technology Office for Chemical and Biological Defense under award number HDTRA1-21-1-0010the National Institutes of Health under Award Numbers R21AI159492 and R21AI175904.
文摘Given their dangerous effects on the nervous system,neurotoxins represent a significant threat to public health.Various therapeutic approaches,including chelating agents,receptor decoys,and toxin-neutralizing antibodies,have been explored.While prophylactic vaccines are desirable,it is oftentimes difficult to effectively balance their safety and efficacy given the highly dangerous nature of neurotoxins.To address this,we report here on a nanovaccine against neurotoxins that leverages the detoxifying properties of cell membrane-coated nanoparticles.A genetically modified cell line with constitutive overexpression of theα7 nicotinic acetylcholine receptor is developed as a membrane source to generate biomimetic nanoparticles that can effectively and irreversibly bind toα-bungarotoxin,a model neurotoxin.This abrogates the biological activity of the toxin,enabling the resulting nanotoxoid to be safely delivered into the body and processed by the immune system.When co-administered with an immunological adjuvant,a strong humoral response againstα-bungarotoxin is generated that protects vaccinated mice against a lethal dose of the toxin.Overall,this work highlights the potential of using genetic modification strategies to develop nanotoxoid formulations against various biological threats.
