Plasmid DNA Production for Therapeutic Applications
Plasmid DNA Production for Therapeutic Applications
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DOI：
10.1007/978-1-61779-433-9_14
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发表时间：
2012-01-01
期刊：
影响因子：
--
通讯作者：
Ramirez, Octavio T.
中科院分区：
文献类型：
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作者：
Lara, Alvaro R.;Ramirez, Octavio T.
质粒DNA （pDNA）是有前途的DNA疫苗和基因疗法的基础，用于治疗许多传染性、获得性和遗传性疾病，包括艾滋病毒艾滋病、埃博拉病毒、疟疾和不同类型的癌症、肠道病原体和流感。与传统疫苗相比，DNA疫苗具有稳定性高、不具有传染性、仅将免疫反应集中于需要免疫的抗原以及疫苗保护的长期持久性等优点。特别是在发展中国家，传统的有效疫苗往往无法获得或过于昂贵，因此需要新的和改进的疫苗。因此，在不久的将来，pDNA的需求预计将大幅上升。由于注射pDNA通常只会导致较弱的免疫反应，因此需要几毫克的DNA疫苗来进行免疫保护。因此，为了降低制造成本，提高产品产量是一种特殊的兴趣。在本章中，回顾了质粒DNA生产的不同阶段，从载体设计到下游操作选择。特别是，最近的进展，细胞工程提高质粒DNA的生产进行了讨论。
Plasmid DNA (pDNA) is the base for promising DNA vaccines and gene therapies against many infectious, acquired, and genetic diseases, including HIV-AIDS, Ebola, Malaria, and different types of cancer, enteric pathogens, and influenza. Compared to conventional vaccines, DNA vaccines have many advantages such as high stability, not being infectious, focusing the immune response to only those antigens desired for immunization and long-term persistence of the vaccine protection. Especially in developing countries, where conventional effective vaccines are often unavailable or too expensive, there is a need for both new and improved vaccines. Therefore the demand of pDNA is expected to rise significantly in the near future. Since the injection of pDNA usually only leads to a weak immune response, several milligrams of DNA vaccine are necessary for immunization protection. Hence, there is a special interest to raise the product yield in order to reduce manufacturing costs. In this chapter, the different stages of plasmid DNA production are reviewed, from the vector design to downstream operation options. In particular, recent advances on cell engineering for improving plasmid DNA production are discussed.