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Extracellular vesicles incorporating retrovirus-like capsids for the enhanced packaging and systemic delivery of mRNA into neurons

Nat Biomed Eng. 2024-02; 
Wenchao Gu, Sijin Luozhong, Simian Cai, Ketaki Londhe, Nadine Elkasri, Robert Hawkins, Zhefan Yuan, Kai Su-Greene, Yujie Yin, Margaret Cruz, Yu-Wei Chang, Patrick McMullen, Chunyan Wu, Changwoo Seo, Akash Guru, Wenting Gao, Tara Sarmiento, Chris Schaffer, Nozomi Nishimura, Richard Cerione, Qiuming Yu, Melissa Warden, Robert Langer, Shaoyi Jiang
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Gene Synthesis … choice, given the potential loss of critical components for Arc EV assembly and functionality. … The rat Arc 5’ UTR sequence was synthesized by Genscript. Molecular cloning techniques (… Get A Quote

摘要

The blood-brain barrier (BBB) restricts the systemic delivery of messenger RNAs (mRNAs) into diseased neurons. Although leucocyte-derived extracellular vesicles (EVs) can cross the BBB at inflammatory sites, it is difficult to efficiently load long mRNAs into the EVs and to enhance their neuronal uptake. Here we show that the packaging of mRNA into leucocyte-derived EVs and the endocytosis of the EVs by neurons can be enhanced by engineering leucocytes to produce EVs that incorporate retrovirus-like mRNA-packaging capsids. We transfected immortalized and primary bone-marrow-derived leucocytes with DNA or RNA encoding the capsid-forming activity-regulated cytoskeleton-associated (Arc) protein as well as capsid-s... More

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