Plasmid DNA vaccine vector design: impact on efficacy, safety and upstream production.
Plasmid DNA vaccine vector design: impact on efficacy, safety and upstream production.
复制标题
DOI：
10.1016/j.biotechadv.2009.02.003
复制
发表时间：
2009-07
影响因子：
16
通讯作者：
Hodgson, Clague P.
中科院分区：
文献类型：
--
作者：
Williams, James A.;Carnes, Aaron E.;Hodgson, Clague P.
综述了影响可许可DNA疫苗载体设计的关键分子和细胞生物学因素，这种载体结合了细菌生产过程中的高产率和完整性，并增加了在哺乳动物细胞中的表达。讨论了食品和药物管理局(FDA)、世界卫生组织(WHO)和欧洲医疗机构(EMEA)的监管指南，因为它们与载体设计和质粒发酵有关。虽然所有新载体在临床使用之前都需要广泛的临床前测试来验证安全性和性能，但通过将精心设计的合成基因与现有经过验证的载体骨架相结合，可以减轻后续产品的监管测试负担。结合原理设计和生物信息学，给出了创造新的合成基因的流程图。回顾了质粒复制的生物学，并讨论了降低代谢负担的过程工程策略。利用最近开发的低代谢负荷的种源和发酵策略，优化的载体现在可以制造出产量超过2g/L的高产量，特定的质粒产量为总细胞干重的5%。
Critical molecular and cellular biological factors impacting design of licensable DNA vaccine vectors that combine high yield and integrity during bacterial production with increased expression in mammalian cells are reviewed. Food and Drug Administration (FDA), World Health Organization (WHO) and European Medical Agencies (EMEA) regulatory guidance’s are discussed, as they relate to vector design and plasmid fermentation. While all new vectors will require extensive preclinical testing to validate safety and performance prior to clinical use, regulatory testing burden for follow-on products can be reduced by combining carefully designed synthetic genes with existing validated vector backbones. A flowchart for creation of new synthetic genes, combining rationale design with bioinformatics, is presented. The biology of plasmid replication is reviewed, and process engineering strategies that reduce metabolic burden discussed. Utilizing recently developed low metabolic burden seed stock and fermentation strategies, optimized vectors can now be manufactured in high yields exceeding 2 g/L, with specific plasmid yields of 5% total dry cell weight.
登录
查看更多内容
影响因子：
12.4
作者：
Chen, Zhi-Ying;Riu, Efren;Kay, Mark A.
通讯作者：
Kay, Mark A.
影响因子：
3.5
作者：
Bloquel, C;Fabre, E;Scherman, D
通讯作者：
Scherman, D
DOI：
10.1006/bbrc.2000.3603
发表时间：
2000-10-05
影响因子：
3.1
作者：
Allamane, S;Jourdes, P;Wion, D
通讯作者：
Wion, D
影响因子：
3.5
作者：
Azzoni, Adriano R.;Ribeiro, Sofia C.;Prazeres, Duarte M. F.
通讯作者：
Prazeres, Duarte M. F.
影响因子：
--
作者：
Carnes, Aaron E;Williams, James A
通讯作者：
Williams, James A