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Exosome delivery to the testes for dmrt1 suppression: A powerful tool for sex-determining gene studies

文献类型： 外文期刊

作者： Zhu, Tengfei 1 ; Kong, Ming 3 ; Yu, Yingying 4 ; Schartl, Manfred 5 ; Power, Deborah Mary 7 ; Li, Chen 1 ; Ma, Wenxiu 1 ; Sun, Yanxu 1 ; Li, Shuo 1 ; Yue, Bowen 1 ; Li, Weijing 1 ; Shao, Changwei 1 ;

作者机构： 1.Chinese Acad Fishery Sci, Yellow Sea Fisheries Res Inst, Natl Key Lab Mariculture Biobreeding & Sustainable, Nanjing Rd 106, Qingdao 266071, Peoples R China

2.Qingdao Natl Lab Marine Sci & Technol, Lab Marine Fisheries Sci & Food Prod Proc, Wenhaizhong Rd 168, Qingdao 266237, Peoples R China

3.Ocean Univ China, Coll Marine Life Sci, Yushan Rd 5, Qingdao 266003, Peoples R China

4.Foshan Univ, Sch Life Sci & Engn, Guangdong Prov Key Lab Anim Mol Design & Precise B, Guangyun Rd 33, Foshan 528225, Peoples R China

5.Univ Wurzburg, Dev Biochem, Bioctr, Sanderring 2, D-97074 Wurzburg, Germany

6.Texas State Univ, Xiphophorus Genet Stock Ctr, Dept Chem & Biochem, 601 Univ Dr, San Marcos, TX 78666 USA

7.Univ Algarve, Ctr Marine Sci, Comparat Endocrinol & Integrat Biol, Campus Gambelas, P-8005139 Faro, Portugal

8.Chinese Acad Fishery Sci, Yellow Sea Fisheries Res Inst, Key Lab Maricultural Organism Dis Control, Qingdao Key Lab Mariculture Epidemiol & Biosecur,M, Nanjing Rd 106, Qingdao 266072, Peoples R China

关键词： Engineered exosome; Delivery system; Tissue targeting; dmrt1; Sex-determining gene; microRNA

期刊名称：JOURNAL OF CONTROLLED RELEASE （ 影响因子：10.8； 五年影响因子：10.2 ）

ISSN： 0168-3659

年卷期： 2023 年 363 卷

页码：

收录情况： SCI

摘要： 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 of dmrt1, 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 a dmrt1 inhibitor 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 that dmrt1 played important roles in maintaining the regular structure and function of testis in juvenile fish. This is the first de novo development of an exosome-based delivery system applied in the study of sexdetermining gene, which indicates an attractive prospect for the future applications of engineered exosomes in exploring more extensive biological conundrums.

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