Sharp Brenna, Rallabandi Ramya, Devaux Patricia
Department of Molecular Medicine, Mayo Clinic, Rochester, MN, 55905, USA.
Virology and Gene Therapy Graduate Program, Mayo Clinic, Rochester, MN, USA.
Mol Diagn Ther. 2022 Jul;26(4):353-367. doi: 10.1007/s40291-022-00599-x. Epub 2022 Jun 28.
Ethical issues are a significant barrier to the use of embryonic stem cells in patients due to their origin: human embryos. To further the development of stem cells in a patient application, alternative sources of cells were sought. A process referred to as reprogramming was established to create induced pluripotent stem cells from somatic cells, resolving the ethical issues, and vectors were developed to deliver the reprogramming factors to generate induced pluripotent stem cells. Early viral vectors used integrating retroviruses and lentiviruses as delivery vehicles for the transcription factors required to initiate reprogramming. However, because of the inherent risk associated with vectors that integrate into the host genome, non-integrating approaches were explored. The development of non-integrating viral vectors offers a safer alternative, and these modern vectors are reliable, efficient, and easy to use to achieve induced pluripotent stem cells suitable for direct patient application in the growing field of individualized medicine. This review summarizes all the RNA viral vectors in the field of reprogramming with a special focus on the emerging delivery vectors based on non-integrating Paramyxoviruses, Sendai and measles viruses. We discuss their design and evolution towards being safe and efficient reprogramming vectors in generating induced pluripotent stem cells from somatic cells.
伦理问题是胚胎干细胞应用于患者的重大障碍，这是由于其来源为人类胚胎。为了推动干细胞在患者应用方面的发展，人们寻找细胞的替代来源。建立了一种称为重编程的过程，从体细胞中创建诱导多能干细胞，解决了伦理问题，并且开发了载体来递送重编程因子以生成诱导多能干细胞。早期的病毒载体使用整合型逆转录病毒和慢病毒作为启动重编程所需转录因子的递送载体。然而，由于与整合到宿主基因组中的载体相关的固有风险，人们探索了非整合方法。非整合病毒载体的开发提供了一种更安全的选择，并且这些现代载体可靠、高效且易于使用，以实现适合在个性化医学这一不断发展的领域中直接应用于患者的诱导多能干细胞。本综述总结了重编程领域中的所有RNA病毒载体，特别关注基于非整合型副粘病毒、仙台病毒和麻疹病毒的新兴递送载体。我们讨论了它们在从体细胞生成诱导多能干细胞方面朝着成为安全高效的重编程载体的设计和演变。
