Selective Encapsulation of Therapeutic mRNA in Engineered Extracellular Vesicles by DNA Aptamer
Abstract
Extracellular vesicles (EV)-based delivery of therapeutic mRNAs is challenged by the low loading efficiency. In this study, we designed a DNA aptamer consisting of two parts: the single strand part recognized the AUG region of target mRNA, preventing mRNA from translation and ribosome assembly; and the double strand part containing the elements recognized by the CD9-ZF (zinc finger) motifs, sorting DNA aptamer-mRNA complex into CD9-ZF engineered EVs. In vitro and in vivo studies revealed that the system could efficiently load functional mRNAs to the EVs. Furthermore, adipose specific delivery of loaded Pgc1α mRNA via the strategy could efficiently induce white adipocyte browning. Similarly, delivery of interleukin-10 ( Il- 10) mRNA via the strategy had potent anti-inflammatory effect in inflammatory bowel disease (IBD) mouse model. Together, our study has proposed an efficient strategy to load therapeutic mRNAs of interest into EVs, which could be used as a promising strategy for gene therapy.
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The same system demonstrated an effective anti-inflammatory effect in an inflammatory bowel disease (IBD) mouse model upon the delivery of interleukin 10 mRNA.
“Similarly, the system demonstrated an effective anti-inflammatory effect in an inflammatory bowel disease (IBD) mouse model upon the delivery of interleukin 10 mRNA [104].”
From Exosome for mRNA delivery: Strategies and therapeutic applications (2024) · cites this paper as [104]
A two-part DNA aptamer strategy efficiently delivered loaded Pgc1α mRNA to induce the browning of white adipocytes.
“This strategy efficiently delivered loaded Pgc1α mRNA to induce the browning of white adipocytes.”
From Exosome for mRNA delivery: Strategies and therapeutic applications (2024) · cites this paper as [104]
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Exosome for mRNA delivery: Strategies and therapeutic applications
Iqbal, Z., Rehman, K., Mahmood, A., Shabbir, M., Liang, Y., Duan, L., & Zeng, H. (2024) · Journal of Nanobiotechnology · doi:10.1186/s12951-024-02634-x · Cited by 144 · see citing works
- Authors
- Zhang, S., Dong, Y., Wang, Y., Sun, W., Wei, M., Yuan, L., & Yang, G.
- Affiliations
- Tang Du Hospital (CN)
- Air Force Medical University (CN)
- Corresponding author
- Yuan, Lijun
- Yang, Guodong
- Venue
- Nano Letters
- Publisher
- American Chemical Society (ACS)
- Published
- 2021-10-14
- Volume
- 21
- Issue
- 20
- Pages
- 8563-8570
- ISSN
- 1530-6984 (ISSN-L)
- 1530-6992
- OpenAlex
- W3207043397
- Cited by
- 50
- References
- 26
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 13 · 2023: 15 · 2022: 11
- FWCI
- 3.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Nano Letters (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (31771507, 81671690, 81871357, 81970737)
- Provincial Scientific Foundation of Shaan???Xi (2020TD-038)
- Tangdu Hospital (2018QYTS007)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- extracellular vesicles, mRNA encapsulation, DNA aptamers, PGC-1α, white adipocyte browning, IL-10, inflammatory bowel disease, anti-inflammatory gene therapy
- MeSH terms
- Extracellular Vesicles, Animals, Cell Movement, Disease Models, Animal, RNA, Messenger, Mice, Aptamers, Nucleotide
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