Exosome delivery to the testes for dmrt1 suppression: A powerful tool for sex-determining gene studies.
Exosome delivery to the testes for dmrt1 suppression: A powerful tool for sex-determining gene studies.
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DOI：
10.1016/j.jconrel.2023.09.027
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发表时间：
2023-09
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影响因子：
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通讯作者：
Tengfei Zhu;Ming Kong;Yingying Yu;Manfred Schartl;Deborah Mary Power;Chen Li;Wenxiu Ma;Yanxu Sun;Shuo Li;Bowen Yue;Weijing Li;Changwei Shao
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作者：
Tengfei Zhu;Ming Kong;Yingying Yu;Manfred Schartl;Deborah Mary Power;Chen Li;Wenxiu Ma;Yanxu Sun;Shuo Li;Bowen Yue;Weijing Li;Changwei Shao
外泌体是直径约100 nm的内体衍生的细胞外囊泡。由于它们在生物相容性和工程性方面的优势，它们正在成为有前途的递送平台。然而，对工程化外泌体的研究和应用仍然限于哺乳动物的少数医学领域。在这里，我们将其应用范围扩大到早期脊椎动物性别决定基因的研究。为有效调控多细胞动物中最广泛使用的性别决定基因之一dmrt 1，开发了一种构建基于外泌体的递送系统的整合策略。通过结合分子生物学经典方法和生物信息学最新技术，将isomiR-124 a作为admrt 1抑制剂，负载到exosomes中，并利用睾丸靶向肽修饰exosomes表面，以实现高效递送。结果表明，异miR-124 a基因可通过外源基因转染的方式有效地传递到幼鱼精巢中，并揭示了dmrt 1在幼鱼精巢正常结构和功能维持中的重要作用。这是首次将外泌体导入性别决定基因的研究中，为外泌体工程在探索更广泛的生物学难题方面的应用展示了诱人的前景。
Exosomes are endosome-derived extracellular vesicles about 100 nm in diameter. They are emerging as promising delivery platforms due to their advantages in biocompatibility and engineerability. However, research into and applications for engineered exosomes are still limited to a few areas of medicine in mammals. Here, we expanded the scope of their applications to sex-determining gene studies in early vertebrates. An integrated strategy for constructing the exosome-based delivery system was developed for efficient regulation ofdmrt1, which is one of the most widely used sex-determining genes in metazoans. By combining classical methods in molecular biology and the latest technology in bioinformatics, isomiR-124a was identified as admrt1inhibitor and was loaded into exosomes and a testis-targeting peptide was used to modify exosomal surface for efficient delivery. Results showed that isomiR-124a was efficiently delivered to the testes by engineered exosomes and revealed thatdmrt1played important roles in maintaining the regular structure and function of testis in juvenile fish. This is the firstde novodevelopment of an exosome-based delivery system applied in the study of sex-determining gene, which indicates an attractive prospect for the future applications of engineered exosomes in exploring more extensive biological conundrums.