The fibroblast is one of the ideal target cell candidates for cell-based gene therapy approaches to promote tissue repair. Gene delivery to fibroblasts by viral transfection has been confirmed to have high transfection efficiency. However, in addition to immunogenic effects of viruses, the random integration of viral genes may damage the genome, affect the cell phenotype or even cause cancerous mutations in the transfected cells. Due to these potential biohazards and unknown long-term risks, the clinical use of viral transfection has been very limited. In contrast, initial non-viral transfection methods have been simple and safe to implement, with low immunogenicity, insertional mutagenesis, and risk of carcinogenesis, but their transfection efficiency has been relatively low. Nucleofection, a more recent non-viral transfection method, now combines the advantages of high transfection efficiency and direct nucleic acid delivery to the nucleus with a high safety. Here, we reviewed recent articles on fibroblast nucleofection, summarized different research points, improved methods and application scopes, and opened up ideas for promoting the further improvement and development of fibroblast nucleofection to meet the needs of a variety of disease research and clinical applications.

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核酸直接递送至成纤维细胞：核转染及其应用综述

成纤维细胞是基于细胞的基因治疗方法促进组织修复的理想靶细胞候选者之一。已证实通过病毒转染将基因递送至成纤维细胞具有高转染效率。然而，除了病毒的免疫原性作用外，病毒基因的随机整合可能会破坏基因组，影响细胞表型甚至导致转染细胞发生癌变。由于这些潜在的生物危害和未知的长期风险，病毒转染的临床应用非常有限。相比之下，最初的非病毒转染方法实施起来简单安全，免疫原性低、插入诱变和致癌风险低，但转染效率相对较低。核转染，一种较新的非病毒转染方法，现在结合了高转染效率和直接将核酸递送到细胞核的优点，安全性高。在此，我们回顾了近期关于成纤维细胞核转染的文章，总结了不同的研究点、改进方法和应用范围，为促进成纤维细胞核转染的进一步完善和发展开辟了思路，以满足多种疾病研究和临床应用的需要。