Department of Material and Bioprocess Engineering, School of Chemical Engineering, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil; Institute of Biomedical Engineering, Old Road Campus Research Building, University of Oxford, Headington, Oxford OX3 7DQ, UK.
Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Biotechnol Adv. 2024 May-Jun;72:108342. doi: 10.1016/j.biotechadv.2024.108342. Epub 2024 Mar 20.
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.
基因组缺陷会导致遗传疾病，可以通过基因治疗来治疗。由于在基因传递中遇到的限制，基于脂质的超分子胶体材料已经成为有前途的基因载体系统。在未功能化的形式下，脂质纳米粒通常表现出较低的转基因表达效率，导致治疗效果不理想，特别是通过降低表达转基因的细胞的百分比。由于化学活性取代基，具有特定化学配体的遗传药物的递送系统的工程设计作为一种创新策略向前推进，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研究，但此类疗法的临床结果仍有待改善。在这里，我们重点介绍并全面回顾了用于功能化基于脂质的递药系统的工程学方面及其用于开发新型遗传有效载荷的治疗功效，以提供从实验室到临床的全面转化情况。我们概述了递药和内化过程中存在的挑战，并讲述了最近在用于核酸的基于脂质的递药系统的功能化方面的进展，以提高其治疗功效和安全性。此外，我们还讨论了使用这些载体进行的临床试验，以扩大其临床应用和主要安全性问题。
