Translational Advances of Hydrofection by Hydrodynamic Injection.
Translational Advances of Hydrofection by Hydrodynamic Injection.
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DOI：
10.3390/genes9030136
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发表时间：
2018-03-01
期刊：
影响因子：
3.5
通讯作者：
Aliño SF
中科院分区：
文献类型：
--
作者：
Sendra L;Herrero MJ;Aliño SF
水动力基因传递已被证明是一种安全有效的基因转移方法，能够在小鼠模型中介导转染基因编码的蛋白质的治疗水平。在不同的疾病模型和针对不同的器官，它已被证明可以恢复病理症状和体征。积液的治疗潜力使不同的小组致力于该程序的临床翻译。为了防止因大剂量快速注射而产生的血流动力学副作用，必须调节条件，使其与中型动物模型（如大鼠、仓鼠和兔子）和大型动物（如狗、猪和灵长类动物）的使用相适应。尽管采用了不同的方法来适应基因传递的条件，但在这些中型和大型动物中获得的结果都比在小鼠模型中获得的结果要差。在这些减少体积的不同策略中，最有效的策略是排除目标器官的脉管系统并直接注射溶液。通过在大型动物中进行导管置入和外科手术，该方法已允许在组织中实现接近金标准模型的蛋白质表达水平。这些有希望的结果和利用这些策略转移能够编辑基因的基因结构的可能性，如CRISPR，重新燃起了这种基因转移过程的临床兴趣。为了将水动力基因传递转化为人类使用，需要标准化的程序条件和评估的分子参数，以便能够比较结果并建立一种表达所获得数据的均匀方式，作为“经典”药物。
Hydrodynamic gene delivery has proven to be a safe and efficient procedure for gene transfer, able to mediate, in murine model, therapeutic levels of proteins encoded by the transfected gene. In different disease models and targeting distinct organs, it has been demonstrated to revert the pathologic symptoms and signs. The therapeutic potential of hydrofection led different groups to work on the clinical translation of the procedure. In order to prevent the hemodynamic side effects derived from the rapid injection of a large volume, the conditions had to be moderated to make them compatible with its use in mid-size animal models such as rat, hamster and rabbit and large animals as dog, pig and primates. Despite the different approaches performed to adapt the conditions of gene delivery, the results obtained in any of these mid-size and large animals have been poorer than those obtained in murine model. Among these different strategies to reduce the volume employed, the most effective one has been to exclude the vasculature of the target organ and inject the solution directly. This procedure has permitted, by catheterization and surgical procedures in large animals, achieving protein expression levels in tissue close to those achieved in gold standard models. These promising results and the possibility of employing these strategies to transfer gene constructs able to edit genes, such as CRISPR, have renewed the clinical interest of this procedure of gene transfer. In order to translate the hydrodynamic gene delivery to human use, it is demanding the standardization of the procedure conditions and the molecular parameters of evaluation in order to be able to compare the results and establish a homogeneous manner of expressing the data obtained, as ‘classic’ drugs.
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影响因子：
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