Engineering human cells for in vivo secretion of antibody and non-antibody therapeutic proteins.
Engineering human cells for in vivo secretion of antibody and non-antibody therapeutic proteins.
复制标题
DOI：
10.1016/j.copbio.2011.03.001
复制
发表时间：
2011-12
影响因子：
7.7
通讯作者：
D. Sánchez-Martín;L. Sanz;L. Álvarez-Vallina
中科院分区：
文献类型：
--
作者：
D. Sánchez-Martín;L. Sanz;L. Álvarez-Vallina
纯化的蛋白质如抗体在临床医学中广泛用作治疗剂。然而，用于治疗用途的临床级蛋白质需要复杂的技术，并且生产成本极高。通过遗传工程改造的人细胞体内分泌治疗性蛋白质可以有利地代替高度纯化的蛋白质的注射。基因转移方法的使用避免了与大规模生产和纯化相关的问题，并通过实现具有同基因糖基化模式的治疗性蛋白质的持续浓度提供了额外的益处，所述同基因糖基化模式使蛋白质潜在地具有较低的免疫原性。通过不同的细胞/组织在体内生产治疗性蛋白质的可行性现在已经使用不同的技术得到了证明，例如离体遗传修饰的细胞和由病毒载体介导的体内基因转移。
Purified proteins such as antibodies are widely used as therapeutic agents in clinical medicine. However, clinical-grade proteins for therapeutic use require sophisticated technologies and are extremely expensive to produce. In vivo secretion of therapeutic proteins by genetically engineered human cells may advantageously replace injection of highly purified proteins. The use of gene transfer methods circumvents problems related to large-scale production and purification and offers additional benefits by achieving sustained concentrations of therapeutic protein with a syngenic glycosylation pattern that make the protein potentially less immunogenic. The feasibility of the in vivo production of therapeutic proteins by diverse cells/tissues has now been demonstrated using different techniques, such as ex vivo genetically modified cells and in vivo gene transfer mediated by viral vectors.