DNA-based therapies are often limited by challenges such as stability, long-term integration, low transfection efficiency, and insufficient targeted DNA delivery. This review focuses on recent progress in the design of non-viral delivery systems for enhancing targeted DNA delivery and modulation of therapeutic efficiency. Cellular uptake and intracellular trafficking mechanisms play a crucial role in optimizing gene delivery efficiency. There are two main strategies employed to improve the efficiency of gene delivery vectors: (i) explore different administration routes (e.g., mucosal, intravenous, intramuscular, subcutaneous, intradermal, intratumoural, and intraocular) that best facilitates optimal uptake into the targeted cells and organs and (ii) modify the delivery vectors with cell-specific ligands (e.g., natural ligands, antibodies, peptides, carbohydrates, or aptamers) that enable targeted uptake to specific cells with higher specificity and improved biodistribution. We describe how recent progress in employing these DNA delivery strategies is advancing the field and increasing the clinical translation and ultimate clinical application of DNA therapies.

中文翻译：

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增强非病毒 DNA 递送系统：提高效率和靶标特异性的最新进展


基于 DNA 的疗法通常受到稳定性、长期整合、转染效率低和靶向 DNA 递送不足等挑战的限制。本文重点介绍了用于增强靶向 DNA 递送和调节治疗效率的非病毒递送系统设计的最新进展。细胞摄取和细胞内运输机制在优化基因递送效率方面起着至关重要的作用。有两种主要策略可用于提高基因递送载体的效率：（i） 探索最能促进目标细胞和器官最佳摄取的不同给药途径（例如，粘膜、静脉内、肌肉内、皮下、皮内、肿瘤内和眼内）和 （ii） 用细胞特异性配体（例如，天然配体、抗体、肽、碳水化合物或适配体）修饰递送载体，使其能够靶向摄取到特定细胞更高的特异性和改进的生物分布。我们描述了采用这些 DNA 递送策略的最新进展如何推动该领域的发展并增加 DNA 疗法的临床转化和最终临床应用。