Defects in the genome cause genetic diseases and can be treated with gene therapy. Due to the limitations encountered in gene delivery, lipid-based supramolecular colloidal materials have emerged as promising gene carrier systems. In their non-functionalized form, lipid nanoparticles often demonstrate lower transgene expression efficiency, leading to suboptimal therapeutic outcomes, specifically through reduced percentages of cells expressing the transgene. Due to chemically active substituents, the engineering of delivery systems for genetic drugs with specific chemical ligands steps forward as an innovative strategy to tackle the drawbacks and enhance their therapeutic efficacy. Despite intense investigations into functionalization strategies, the clinical outcome of such therapies still needs to be improved. Here, we highlight and comprehensively review engineering aspects for functionalizing lipid-based delivery systems and their therapeutic efficacy for developing novel genetic cargoes to provide a full snapshot of the translation from the bench to the clinics. We outline existing challenges in the delivery and internalization processes and narrate recent advances in the functionalization of lipid-based delivery systems for nucleic acids to enhance their therapeutic efficacy and safety. Moreover, we address clinical trials using these vectors to expand their clinical use and principal safety concerns.

中文翻译：

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基于脂质的递送系统的工程方面：体内基因递送、安全标准和翻译策略


基因组缺陷会导致遗传性疾病，可以通过基因疗法进行治疗。由于基因传递中遇到的限制，基于脂质的超分子胶体材料已成为有前途的基因载体系统。在非功能化形式下，脂质纳米颗粒通常表现出较低的转基因表达效率，导致治疗结果不佳，特别是通过表达转基因的细胞百分比减少。由于具有化学活性取代基，具有特定化学配体的基因药物递送系统的工程作为一种创新策略向前迈进，以解决这些缺点并提高其治疗效果。尽管对功能化策略进行了深入的研究，但此类疗法的临床结果仍然需要改进。在这里，我们重点介绍并全面回顾了基于脂质的递送系统功能化的工程方面及其开发新型遗传货物的治疗功效，以提供从实验室到临床的转化的完整快照。我们概述了递送和内化过程中现有的挑战，并叙述了基于脂质的核酸递送系统功能化的最新进展，以提高其治疗功效和安全性。此外，我们还利用这些载体进行临床试验，以扩大其临床用途和主要安全问题。