Construction of a novel Staphylokinase (SAK) mutant with low immunogenicity and its evaluation in rhesus monkey.
Construction of a novel Staphylokinase (SAK) mutant with low immunogenicity and its evaluation in rhesus monkey.
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新型低免疫原性葡萄激酶（SAK）突变体的构建及其在恒河猴中的评价。
DOI：
10.1016/j.ijbiomac.2019.09.191
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发表时间：
2019-11
影响因子：
8.2
通讯作者：
Xu Donggang
中科院分区：
文献类型：
--
作者：
Wang Min;Chen Yao;Fu Wenliang;Zou Minji;Wang Yuanyuan;Xing Weiwei;Wang Jiaxi;Xu Donggang
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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DOI：
10.1007/978-3-642-29627-7_19
发表时间：
2012-04
期刊：
--
影响因子：
--
作者：
Andrew S. Parker;K. Griswold;C. Bailey-Kellogg
通讯作者：
Andrew S. Parker;K. Griswold;C. Bailey-Kellogg
DOI：
--
发表时间：
1998
期刊：
Bulletin of the Academy of Military Medical Sciences
影响因子：
--
作者：
M. Zou;Jiaxi Wang;Chunwen Zhao;Lihong Wang;J. Duan
通讯作者：
M. Zou;Jiaxi Wang;Chunwen Zhao;Lihong Wang;J. Duan
DOI：
--
发表时间：
2004
期刊：
--
影响因子：
--
作者：
Li Wu
通讯作者：
Li Wu
影响因子：
2.9
作者：
O. Saksela
通讯作者：
O. Saksela
影响因子：
6.7
作者：
Laurent Jespers;Sophie Vanwetswinkel;H. Lijnen;N. V. Herzeele;B. Hoef;E. Demarsin;D. Collen;M. Maeyer
通讯作者：
Laurent Jespers;Sophie Vanwetswinkel;H. Lijnen;N. V. Herzeele;B. Hoef;E. Demarsin;D. Collen;M. Maeyer