Department of Cell Biology, Cancer Center, Warsaw, Poland.
Adv Clin Exp Med. 2012 Jul-Aug;21(4):525-34.
Gene therapy is recognized to be a novel method for the treatment of various disorders. Gene therapy strategies involve gene manipulation on broad biological processes responsible for the spreading of diseases. Cancer, monogenic diseases, vascular and infectious diseases are the main targets of gene therapy. In order to obtain valuable experimental and clinical results, sufficient gene transfer methods are required. Therapeutic genes can be administered into target tissues via gene carriers commonly defined as vectors. The retroviral, adenoviral and adeno-associated virus based vectors are most frequently used in the clinic. So far, gene preparations may be administered directly into target organs or by intravenous, intramuscular, intratumor or intranasal injections. It is common knowledge that the number of gene therapy clinical trials has rapidly increased. However, some limitations such as transfection efficiency and stable and long-term gene expression are still not resolved. Consequently, great effort is focused on the evaluation of new strategies of gene delivery. There are many expectations associated with intranasal delivery of gene preparations for the treatment of diseases. Intranasal delivery of therapeutic genes is regarded as one of the most promising forms of pulmonary gene therapy research. Gene therapy based on inhalation of gene preparations offers an alternative way for the treatment of patients suffering from such lung diseases as cystic fibrosis, alpha-1-antitrypsin defect, or cancer. Experimental and first clinical trials based on plasmid vectors or recombinant viruses have revealed that gene preparations can effectively deliver therapeutic or marker genes to the cells of the respiratory tract. The noninvasive intranasal delivery of gene preparations or conventional drugs seems to be very encouraging, although basic scientific research still has to continue.
基因治疗被认为是治疗各种疾病的一种新方法。基因治疗策略涉及对负责疾病传播的广泛生物过程进行基因操作。癌症、单基因疾病、血管和传染病是基因治疗的主要目标。为了获得有价值的实验和临床结果,需要充足的基因转移方法。治疗性基因可以通过通常定义为载体的基因载体递送到靶组织。基于逆转录病毒、腺病毒和腺相关病毒的载体在临床上最常用。到目前为止,基因制剂可以直接递送到靶器官,也可以通过静脉内、肌肉内、肿瘤内或鼻内注射递送到靶器官。众所周知,基因治疗临床试验的数量迅速增加。然而,一些限制,如转染效率和稳定、长期的基因表达,仍然没有得到解决。因此,人们致力于评估新的基因传递策略。基因制剂经鼻腔给药治疗疾病有很多期望。将治疗性基因经鼻腔给药被认为是肺基因治疗研究中最有前途的形式之一。基于吸入基因制剂的基因治疗为治疗囊性纤维化、α-1-抗胰蛋白酶缺陷或癌症等肺部疾病的患者提供了一种替代方法。基于质粒载体或重组病毒的实验和首次临床试验表明,基因制剂可以有效地将治疗性或标记基因递送到呼吸道细胞中。基因制剂或常规药物的非侵入性经鼻腔给药似乎非常有希望,尽管基础科学研究仍需继续。