Departments of Pediatrics and Biomedical Engineering, University of Rochester, 601 Elmwood Avenue, Rochester, NY, 14642, USA,
J Membr Biol. 2013 Oct;246(10):737-44. doi: 10.1007/s00232-013-9534-y. Epub 2013 Mar 24.
The use of electroporation to facilitate gene transfer is an extremely powerful and useful method for both in vitro and in vivo applications. One of its great strengths is that it induces functional destabilization and permeabilization of cell membranes throughout a tissue leading to widespread gene transfer to multiple cells and cell types within the electric field. While this is a strength, it can also be a limitation in terms of cell-specific gene delivery. The ability to restrict gene delivery and expression to particular cell types is of paramount importance for many types of gene therapy, since ectopic expression of a transgene could lead to deleterious host inflammatory responses or dysregulation of normal cellular functions. At present, there are relatively few ways to obtain cell-specific targeting of nonviral vectors, molecular probes, small molecules, and imaging agents. We have developed a novel means of restricting gene delivery to desired cell types based on the ability to control the transport of plasmids into the nuclei of desired cell types. In this article, we discuss the mechanisms of this approach and several applications in living animals to demonstrate the benefits of the combination of electroporation and selective nuclear import of plasmids for cell-specific gene delivery.
电穿孔促进基因转移的应用是一种非常强大且有用的方法，可用于体外和体内应用。它的一个巨大优势是，它会导致整个组织中的细胞膜功能不稳定和通透性增加，从而在电场中将基因广泛转移到多个细胞和细胞类型中。虽然这是一个优势，但就细胞特异性基因传递而言，这也可能是一个限制。对于许多类型的基因治疗来说，将基因传递和表达限制在特定的细胞类型是至关重要的，因为转基因的异位表达可能导致宿主产生有害的炎症反应或正常细胞功能失调。目前，获得非病毒载体、分子探针、小分子和成像剂的细胞特异性靶向的方法相对较少。我们已经开发了一种新的方法，可以根据控制质粒进入所需细胞类型细胞核的能力来限制基因传递到特定细胞类型。在本文中，我们讨论了这种方法的机制，并在活体动物中进行了几种应用，以证明电穿孔和质粒选择性核导入相结合用于细胞特异性基因传递的优势。
