Genetic engineering of stem cells for enhanced therapy.
Genetic engineering of stem cells for enhanced therapy.
复制标题
DOI：
10.55782/ane-2013-1918
复制
发表时间：
2013-01-01
影响因子：
1.4
通讯作者：
Lukomska, Barbara
中科院分区：
文献类型：
--
作者：
Nowakowski, Adam;Andrzejewska, Anna;Lukomska, Barbara
干细胞治疗是克服当前治疗方法局限性的一种很有前途的策略。干细胞特性的改变可能是充分开发其潜力所必需的。基因工程具有丰富的方法，能够以精确和可控的方式诱导基因表达，因此对这一目的特别有吸引力。基因操作有基于病毒的方法和非病毒的方法。基因组整合病毒载体的特点通常是高效和长期的转基因表达，但以安全为代价。非整合病毒在转导方面也很高效，虽然更安全，但只提供有限的转基因表达时间。核酸的可转化形式有很大的多样性；然而，为了有效地穿梭于细胞膜之间，需要额外的操作。为此，采用了物理和化学两种方法。干细胞工程在临床上的应用仍处于初级阶段，需要进一步研究。在治疗性细胞中诱导转基因表达主要有两种策略：瞬时表达和永久表达。在许多情况下，包括干细胞贩运和使用细胞疗法治疗短愈合过程中的快速发病疾病，瞬时转基因表达可能是一种充分和最佳的方法。为此，基于信使核糖核酸的方法似乎是理想的选择，因为它们的特点是快速、高效、安全。永久性转基因表达主要基于病毒载体的应用，出于安全考虑，这些方法更具挑战性。目前正在进行积极的研究，以开发能够诱导永久表达的非病毒方法，如转座子和哺乳动物人工染色体。
Stem cell therapy is a promising strategy for overcoming the limitations of current treatment methods. The modification of stem cell properties may be necessary to fully exploit their potential. Genetic engineering, with an abundance of methodology to induce gene expression in a precise and well-controllable manner, is particularly attractive for this purpose. There are virus-based and non-viral methods of genetic manipulation. Genome-integrating viral vectors are usually characterized by highly efficient and long-term transgene expression, at a cost of safety. Non-integrating viruses are also highly efficient in transduction, and, while safer, offer only a limited duration of transgene expression. There is a great diversity of transfectable forms of nucleic acids; however, for efficient shuttling across cell membranes, additional manipulation is required. Both physical and chemical methods have been employed for this purpose. Stem cell engineering for clinical applications is still in its infancy and requires further research. There are two main strategies for inducing transgene expression in therapeutic cells: transient and permanent expression. In many cases, including stem cell trafficking and using cell therapy for the treatment of rapid-onset disease with a short healing process, transient transgene expression may be a sufficient and optimal approach. For that purpose, mRNA-based methods seem ideally suited, as they are characterized by a rapid, highly efficient transfection, with outstanding safety. Permanent transgene expression is primarily based on the application of viral vectors, and, due to safety concerns, these methods are more challenging. There is active, ongoing research toward the development of non-viral methods that would induce permanent expression, such as transposons and mammalian artificial chromosomes.