Dept Oncology, University of Oxford, Old road Campus, Headington, Oxford OX3 7DQ, United Kingdom.
J Control Release. 2012 Jul 20;161(2):537-53. doi: 10.1016/j.jconrel.2012.02.013. Epub 2012 Feb 18.
Gene delivery remains the greatest challenge in applying nucleic acid therapeutic for a broad range of diseases. Combining stability during the delivery phase with activation and transgene expression following arrival at the target site requires sophisticated vectors that can discriminate between cell types and respond to target-associated conditions to trigger expression. Efficient intravenous delivery is the greatest single hurdle, with synthetic vectors frequently found to be unstable in the harsh conditions of the bloodstream, and viral vectors often recognized avidly by both the innate and the adaptive immune system. Both types of vectors benefit from coating with hydrophilic polymers. Self-assembling polyelectrolyte non-viral vectors can achieve both steric and lateral stabilization following surface coating, endowing them with much improved systemic circulation properties and better access to disseminated targets; similarly viral vectors can be 'stealthed' and their physical properties modulated by surface coating. Both types of vectors may also have their tropism changed following chemical linkage of novel ligands to the polymer coating. These families of vectors go some way towards realizing the goal of efficient systemic delivery of genes and should find a range of important uses in bringing this still-emerging field to fruition.
基因传递仍然是将核酸治疗广泛应用于各种疾病的最大挑战。在传递阶段保持稳定性，同时在到达靶位后激活和转基因表达，这需要复杂的载体，能够区分细胞类型，并对靶标相关条件做出反应，以触发表达。高效的静脉内给药是最大的单一障碍，合成载体在血液的恶劣条件下经常不稳定，而病毒载体经常被先天和适应性免疫系统强烈识别。这两种类型的载体都受益于亲水聚合物的涂层。自组装聚电解质非病毒载体在表面涂层后可以实现空间和横向稳定，从而赋予它们更好的全身循环特性和更好的扩散靶标进入能力；类似地，病毒载体可以通过表面涂层“隐身”并调节其物理性质。这两种类型的载体在通过化学连接将新配体连接到聚合物涂层后，其趋向性也可能发生变化。这些载体家族在实现高效全身基因传递的目标方面取得了一定的进展，应该在将这一仍在出现的领域推向成熟方面找到广泛的重要用途。
