Engineering Cell‐Free Protein Synthesis for High‐Yield Production and Human Serum Activity Assessment of Asparaginase: Toward On‐Demand Treatment of Acute Lymphoblastic Leukemia

Hunt J. Porter; Wilding Kristen M.; Barnett R. Jordan; Robinson Hannah; Soltani Mehran; Cho Jae Eun; Bundy Bradley C.

摘要

Abstract > Acute lymphocytic leukemia (ALL) is a common childhood cancer in the United States, with over 6000 new cases diagnosed each year. Administration of bacterial asparaginase (ASNase) has improved survival rates to nearly 80%, however these therapeutics have high incidence of immunological neutralization and serum activity must be monitored for most effective treatment regimens. Here, a 72% improvement in cell‐free protein synthesis (CFPS) of FDA approved <sc>l</sc> ‐asparaginase (crisantaspase) is demonstrated by employing an aspartate‐fed‐batch reactor format. A CFPS‐based ASNase activity assay as a tool for therapeutic regimentation and production quality control is also presented. This work suggests that shelf‐stable and low‐cost Escherichia coli ‐based CFPS reactions may be employed on‐demand to 1) synthesize biologics on‐site for patient administration, 2) verify biologic activity for dosage calculations, and 3) monitor therapeutic activity in human serum during the treatment regimen. The combination of both therapeutic production and activity assessment introduces a concept of synergistic utility for bacterial cell lysates in modern medical treatment. Indeed, recent work with CFPS biosensors supports a not‐too‐distant future when shelf‐stable E. coli CFPS systems are used to diagnose, treat, and monitor treatment of diseases in the clinical setting. </abstract> </span> <span class="z_kbtn z_kbtnclass hoverxs" style="display: none;">展开▼</span> </div> <div class="translation abstracttxt"> <span class="zhankaihshouqi fivelineshidden" id="abstract"> <span>机译：</span><Abstract Type =“Main”XML：Lang =“en”> <标题类型=“main”>抽象</ title> > 急性淋巴细胞白血病（全部）是美国常见的儿童癌症，每年诊断出6000多种新病例。施用细菌天冬酰胺酶（Asnase）的存活率提高到近80％，然而，这些治疗剂具有高发生的免疫中和发病率，必须监测血清活性以获得最有效的治疗方案。这里，FDA批准的无细胞蛋白质合成（CFP）的72％改善 <sc> l </ sc> 通过使用天冬氨酸脲批量反应器形式来证明氨化酶（CrisAspase）。还提出了基于CFPS的ASNase活性测定作为治疗机制和生产质量控制的工具。这项工作表明，货架稳定和低成本大肠杆菌</ i> 基于CFPS反应可以按需适用于1）合成患者给药的生物制剂，2）验证剂量计算的生物活性，以及3）治疗方案期间人血清中的治疗活性。治疗生产和活性评估的组合介绍了现代医学治疗中的细菌细胞裂解物协同效用的概念。实际上，近来与CFPS生物传感器的合作支持货架稳定时的不太遥远的未来 e。 Coli </ I> CFPS系统用于诊断，治疗和监测临床环境中疾病的治疗。 </ p> </摘要> </span> <span class="z_kbtn z_kbtnclass hoverxs" style="display: none;">展开▼</span> </div> </div> <div class="record"> <h2 class="all_title" id="enpatent33" > 著录项</h2> <ul> <li> <span class="lefttit">来源</span> <div style="width: 86%;vertical-align: text-top;display: inline-block;"> <a href='/journal-foreign-15025/'>《Biotechnology Journal: Healthcare,Nutrition,Technology 》</a> <b style="margin: 0 2px;">|</b><span>2020年第4期</span><b style="margin: 0 2px;">|</b> <span>共6页</span> </div> </li> <li> <div class="author"> <span class="lefttit">作者</span> <p id="fAuthorthree" class="threelineshidden zhankaihshouqi"> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Hunt J. Porter&option=202" target="_blank" rel="nofollow">Hunt J. Porter;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Wilding Kristen M.&option=202" target="_blank" rel="nofollow">Wilding Kristen M.;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Barnett R. Jordan&option=202" target="_blank" rel="nofollow">Barnett R. Jordan;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Robinson Hannah&option=202" target="_blank" rel="nofollow">Robinson Hannah;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Soltani Mehran&option=202" target="_blank" rel="nofollow">Soltani Mehran;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Cho Jae Eun&option=202" target="_blank" rel="nofollow">Cho Jae Eun;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Bundy Bradley C.&option=202" target="_blank" rel="nofollow">Bundy Bradley C.;</a> </p> <span class="z_kbtnclass z_kbtnclassall hoverxs" id="zkzz" style="display: none;">展开▼</span> </div> </li> <li> <div style="display: flex;"> <span class="lefttit">作者单位</span> <div style="position: relative;margin-left: 3px;max-width: 639px;"> <div class="threelineshidden zhankaihshouqi" id="fOrgthree"> <p>Department of Chemical EngineeringBrigham Young UniversityProvo UT 84602 USA;</p> <p>Department of Chemical EngineeringBrigham Young UniversityProvo UT 84602 USA;</p> <p>Department of Chemical EngineeringBrigham Young UniversityProvo UT 84602 USA;</p> <p>Department of Chemical EngineeringBrigham Young UniversityProvo UT 84602 USA;</p> <p>Department of Chemical EngineeringBrigham Young UniversityProvo UT 84602 USA;</p> <p>Department of Chemical EngineeringBrigham Young UniversityProvo UT 84602 USA;</p> <p>Department of Chemical EngineeringBrigham Young UniversityProvo UT 84602 USA;</p> </div> <span class="z_kbtnclass z_kbtnclassall hoverxs" id="zhdw" style="display: none;">展开▼</span> </div> </div> </li> <li> <span class="lefttit">收录信息</span> <span style="width: 86%;vertical-align: text-top;display: inline-block;"></span> </li> <li> <span class="lefttit">原文格式</span> <span>PDF</span> </li> <li> <span class="lefttit">正文语种</span> <span>eng</span> </li> <li> <span class="lefttit">中图分类</span> <span> <a href="https://www.zhangqiaokeyan.com/clc/180.html" title="生物工程学（生物技术）">生物工程学（生物技术） ;</a></span> </li> <li class="antistop"> <span class="lefttit">关键词</span> <p style="width: 86%;vertical-align: text-top;"> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=asparaginase assay&option=203" rel="nofollow">asparaginase assay;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=cell‐free protein synthesis&option=203" rel="nofollow">cell‐free protein synthesis;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=crisantaspase&option=203" rel="nofollow">crisantaspase;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=human serum&option=203" rel="nofollow">human serum;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=lymphoblastic leukemia&option=203" rel="nofollow">lymphoblastic leukemia;</a> </p> <div class="translation"> 机译：天冬酰胺酶测定;无细胞蛋白质合成;Crisantspase;人血清;淋巴细胞白血病; </div> </li> </ul> </div> </div> <div class="literature cardcommon"> <div class="similarity "> <h3 class="all_title" id="enpatent66">相似文献</h3> <div class="similaritytab clearfix"> <ul> <li class="active" >外文文献</li> <li >中文文献</li> <li >专利</li> </ul> </div> <div class="similarity_details"> <ul > <li> <div> <b>1. </b><a class="enjiyixqcontent" href="/journal-foreign-detail/0704021882590.html">Engineering Cell‐Free Protein Synthesis for High‐Yield Production and Human Serum Activity Assessment of Asparaginase: Toward On‐Demand Treatment of Acute Lymphoblastic Leukemia</a> <b>[J]</b> . <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Hunt J. 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L-Asparaginase - used for effective treatment of tumours, partic. human acute lymphoblastic leukaemia</a> <b>[P]</b> . <span> 外国专利：  PT96037A </span> <span> . 1992-05-29</span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译：脂质体复合物。续L-天冬酰胺酶-用于有效治疗部分肿瘤。人急性淋巴细胞白血病 </span> </p> </li> <li> <div> <b>5. </b><a class="enjiyixqcontent" href="/patent-detail/06130425484806.html">isolated polypeptide, antibodies or fragments thereof, cell, methods of diagnosis and treatment of acute leukemia, blast crisis chronic leukemia and lymphoblastic lymphoma, pharmaceutical compositions and diagnostic kits</a> <b>[P]</b> . <span> 外国专利：  BRPI0611044A2 </span> <span> . 2010-12-14</span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> 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