免疫原性
葡萄激酶
抗原性
表位
异源的
抗体
突变体
体内
生物
突变
病毒学
抗原
分子生物学
化学
重组DNA
基因
免疫学
生物化学
遗传学
作者
Min Wang,Yao Chen,Wenliang Fu,Minji Zou,Yuanyuan Wang,Weiwei Xing,Jiaxi Wang,De-Xiang Xu
标识
DOI:10.1016/j.ijbiomac.2019.09.191
摘要
The heterologous nature of SAK, a thrombolytic drug, elicits high titers of neutralizing antibodies, which limits its clinical use. Here, we aim to establish a SAK mutant with equivalent activity to the wild type but reduced antigenicity, which may allow for multiple injections. Biosun software was used to predict SAK antigenic epitopes, and several main epitopes were modified by gene deletion and mutation. Ten SAK mutants were constructed, and their thrombolytic activity and immunogenicity were analyzed in vitro. SAK6, with a high expression level (45%), similar thrombolytic activity, and lower antibody reaction, was chosen for in vivo analysis in rhesus monkey. In the nearly 8-month experimental period, the antibody level of the SAK6 group was significantly lower than that of the SAK group. Moreover, only 5% of SAK activity was retained, whereas 75.6% of SAK6 activity was retained after incubating with respective antiserum. Overall, these results demonstrated that SAK6, established through comprehensive site-directed mutagenesis program, had identical thrombolytic activity to SAK, low immunogenicity, and less side effects, demonstrating its efficient clinical potential for thrombus disease.
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