Beijing Key Laboratory of Diabetes Prevention and Research, Endocrinology Center, Lu He Hospital, Capital Medical University, Beijing 101149, China.
Laboratory of Brain Development, Institut du Cerveau et de la Moelle Epiniere- ICM, Hospital Pitie-Salpetriere, 75013 Paris, France.
Curr Gene Ther. 2019;19(1):20-30. doi: 10.2174/1566523218666181003125308.
Myocardial infarction (MI) is the most severe ischemic heart disease and directly leads to heart failure till death. Target molecules have been identified in the event of MI including increasing angiogenesis, promoting cardiomyocyte survival, improving heart function and restraining inflammation and myocyte activation and subsequent fibrosis. All of which are substantial in cardiomyocyte protection and preservation of cardiac function.
To modulate target molecule expression, virus and non-virus-mediated gene transfer have been investigated. Despite successful in animal models of MI, virus-mediated gene transfer is hampered by poor targeting efficiency, low packaging capacity for large DNA sequences, immunogenicity induced by virus and random integration into the human genome.
Nanoparticles could be synthesized and equipped on purpose for large-scale production. They are relatively small in size and do not incorporate into the genome. They could carry DNA and drug within the same transfer. All of these properties make them an alternative strategy for gene transfer. In the review, we first introduce the pathological progression of MI. After concise discussion on the current status of virus-mediated gene therapy in treating MI, we overview the history and development of nanoparticle-based gene delivery system. We point out the limitations and future perspective in the field of nanoparticle vehicle.
Ultimately, we hope that this review could help to better understand how far we are with nanoparticle-facilitated gene transfer strategy and what obstacles we need to solve for utilization of nanomedicine in the treatment of MI.
心肌梗死(MI)是最严重的缺血性心脏病,可直接导致心力衰竭直至死亡。在 MI 事件中已经确定了靶分子,包括增加血管生成、促进心肌细胞存活、改善心脏功能以及抑制炎症和心肌细胞激活及随后的纤维化。所有这些对于心肌细胞保护和保留心脏功能都非常重要。
为了调节靶分子的表达,已经研究了病毒和非病毒介导的基因转移。尽管在 MI 的动物模型中取得了成功,但病毒介导的基因转移受到以下因素的阻碍:靶向效率差、大 DNA 序列的包装容量低、病毒引起的免疫原性和随机整合到人类基因组中。
可以合成并专门设计纳米颗粒进行大规模生产。它们的体积相对较小,不会整合到基因组中。它们可以在同一转移中携带 DNA 和药物。所有这些特性使它们成为基因转移的替代策略。在综述中,我们首先介绍了 MI 的病理进展。在简要讨论了病毒介导的基因治疗在治疗 MI 中的现状后,我们综述了基于纳米颗粒的基因传递系统的历史和发展。我们指出了该领域纳米载体的局限性和未来展望。
最终,我们希望这篇综述能够帮助更好地了解我们在纳米颗粒介导的基因转移策略方面的进展程度,以及我们在将纳米医学用于治疗 MI 方面需要解决的障碍。