探索细胞衍生囊泡作为基因编辑有效载荷瞬时传递载体的潜力。
Exploring the potential of cell-derived vesicles for transient delivery of gene editing payloads.
机构信息
CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal; CIBB - Center for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-504 Coimbra, Portugal; Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal; GeneT - Gene Therapy Center of Excellence Portugal, University of Coimbra, Coimbra, Portugal.
CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal; CIBB - Center for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-504 Coimbra, Portugal; Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal; GeneT - Gene Therapy Center of Excellence Portugal, University of Coimbra, Coimbra, Portugal; Center for Genomic Medicine and Department of Pathology, Massachusetts General Hospital, Boston, MA 02115, USA; Department of Pathology, Harvard Medical School, Boston, MA 02114, USA.
出版信息
Adv Drug Deliv Rev. 2024 Aug;211:115346. doi: 10.1016/j.addr.2024.115346. Epub 2024 Jun 6.
Gene editing technologies have the potential to correct genetic disorders by modifying, inserting, or deleting specific DNA sequences or genes, paving the way for a new class of genetic therapies. While gene editing tools continue to be improved to increase their precision and efficiency, the limited efficacy of in vivo delivery remains a major hurdle for clinical use. An ideal delivery vehicle should be able to target a sufficient number of diseased cells in a transient time window to maximize on-target editing and mitigate off-target events and immunogenicity. Here, we review major advances in novel delivery platforms based on cell-derived vesicles - extracellular vesicles and virus-like particles - for transient delivery of gene editing payloads. We discuss major findings regarding packaging, in vivo biodistribution, therapeutic efficacy, and safety concerns of cell-derived vesicles delivery of gene editing cargos and their potential for clinical translation.
基因编辑技术有潜力通过修改、插入或删除特定的 DNA 序列或基因来纠正遗传疾病，为一类新的基因治疗铺平了道路。虽然基因编辑工具在不断改进以提高其精度和效率，但体内传递的有限功效仍然是临床应用的主要障碍。理想的传递载体应该能够在短暂的时间窗口内靶向足够数量的病变细胞，以最大限度地提高靶编辑效率，并减轻脱靶事件和免疫原性。在这里，我们综述了基于细胞衍生囊泡（细胞外囊泡和类病毒颗粒）的新型传递平台的主要进展，用于基因编辑有效载荷的瞬时传递。我们讨论了关于细胞衍生囊泡传递基因编辑货物的包装、体内生物分布、治疗效果和安全性问题的主要发现，以及它们在临床转化方面的潜力。
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