Current status of non-viral gene therapy for CNS disorders.
Current status of non-viral gene therapy for CNS disorders.
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DOI：
10.1080/17425247.2016.1188802
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发表时间：
2016-10
影响因子：
6.6
通讯作者：
Nair M
中科院分区：
文献类型：
--
作者：
Jayant RD;Sosa D;Kaushik A;Atluri V;Vashist A;Tomitaka A;Nair M
病毒载体和非病毒载体已被用作多种中枢神经系统疾病的基因治疗方法。目前，腺相关病毒(AAV)、逆转录病毒、慢病毒、腺病毒和单纯疱疹病毒(HHV)等病毒载体正被用作临床试验水平的基因治疗的成功载体。然而，在使用它们的过程中出现了许多缺点。阳离子聚合物、阳离子脂类、工程聚合物、纳米粒子和裸DNA等非病毒载体提供了更安全的选择，因此可以探索用于治疗目的。这篇综述讨论了不同类型的病毒和非病毒载体用于基因治疗，并探索了使用这些载体进行基因治疗的中枢神经系统疾病的临床试验。重点包括非病毒基因传递及其挑战，改善转染率的可能策略，有关载体使用的监管问题，以及未来临床应用的前景。阳离子脂类和聚合物的转染率可以通过对所用分子的操纵来提高。阳离子脂类的有效性取决于阳离子电荷、饱和度和连接体的稳定性。决定阳离子聚合物效率的因素是总电荷密度、分子质量和分子的复杂性。所有上述参数都必须注意，才能有效地进行基因传递。
Viral and non-viral vectors have been used as methods of delivery in gene therapy for many CNS diseases. Currently, viral vectors such as adeno-associated viruses (AAV), retroviruses, lentiviruses, adenoviruses and herpes simplex viruses (HHV) are being used as successful vectors in gene therapy at clinical trial levels. However, many disadvantages have risen from their usage. Non-viral vectors like cationic polymers, cationic lipids, engineered polymers, nanoparticles, and naked DNA offer a much safer option and can therefore be explored for therapeutic purposes. This review discusses different types of viral and non-viral vectors for gene therapy and explores clinical trials for CNS diseases that have used these types of vectors for gene delivery. Highlights include non-viral gene delivery and its challenges, possible strategies to improve transfection, regulatory issues concerning vector usage, and future prospects for clinical applications. Transfection efficiency of cationic lipids and polymers can be improved through manipulation of molecules used. Efficacy of cationic lipids is dependent on cationic charge, saturation levels, and stability of linkers. Factors determining efficacy of cationic polymers are total charge density, molecular weights, and complexity of molecule. All of the above mentioned parameters must be taken care for efficient gene delivery.