A Thermal and Enzymatic Dual‐Stimuli Responsive DNA‐Based Nanomachine for Controlled mRNA Delivery
Abstract The extreme instability of mRNA makes the practical application of mRNA‐based vaccines heavily rely on efficient delivery system and cold chain transportation. Herein, a DNA‐based nanomachine, which achieves programmed capture, long‐term storage without cryopreservation, and efficient deliv...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-02-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202204905 |
| _version_ | 1797688102217580544 |
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| author | Feng Li Xiaolei Sun Jing Yang Jin Ren Mengxue Huang Shengqi Wang Dayong Yang |
| author_facet | Feng Li Xiaolei Sun Jing Yang Jin Ren Mengxue Huang Shengqi Wang Dayong Yang |
| author_sort | Feng Li |
| collection | DOAJ |
| description | Abstract The extreme instability of mRNA makes the practical application of mRNA‐based vaccines heavily rely on efficient delivery system and cold chain transportation. Herein, a DNA‐based nanomachine, which achieves programmed capture, long‐term storage without cryopreservation, and efficient delivery of mRNA in cells, is developed. The polythymidine acid (Poly‐T) functionalized poly(N‐isopropylacrylamide) (DNA‐PNIPAM) is synthesized and assembled as the central compartment of the nanomachine. The DNA‐PNIPAM nano‐assembly exhibits reversible thermal‐responsive dynamic property: when lower than the low critical solution temperature (LCST, ≈32 °C) of PNIPAM, the DNA‐PNIPAM transforms into extension state to expose the poly‐T, facilitating the hybridization with polyadenylic acid (Poly‐A) tail of mRNA; when higher than LCST, DNA‐PNIPAM re‐assembles and achieves an efficient encapsulation of mRNA. It is remarkable that the DNA‐PNIPAM nano‐assembly realizes long‐term storage of mRNA (≈7 days) at 37 °C. Biodegradable 2‐hydroxypropyltrimethyl ammonium chloride chitosan is assembled on the outside of DNA‐PNIPAM to facilitate the endocytosis of mRNA, RNase‐H mediating mRNA release occurs in cytoplasm, and efficient mRNA translation is achieved. This work provides a new disign principle of nanosystem for mRNA delivery. |
| first_indexed | 2024-03-12T01:26:52Z |
| format | Article |
| id | doaj.art-034bd1cbf6fb4a9aaab30f2c73365b1a |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-03-12T01:26:52Z |
| publishDate | 2023-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-034bd1cbf6fb4a9aaab30f2c73365b1a2023-09-12T14:40:47ZengWileyAdvanced Science2198-38442023-02-01104n/an/a10.1002/advs.202204905A Thermal and Enzymatic Dual‐Stimuli Responsive DNA‐Based Nanomachine for Controlled mRNA DeliveryFeng Li0Xiaolei Sun1Jing Yang2Jin Ren3Mengxue Huang4Shengqi Wang5Dayong Yang6Frontiers Science Center for Synthetic Biology Key Laboratory of Systems Bioengineering (MOE) Institute of Biomolecular and Biomedical Engineering School of Chemical Engineering and Technology Tianjin University Tianjin 300350 P. R. ChinaFrontiers Science Center for Synthetic Biology Key Laboratory of Systems Bioengineering (MOE) Institute of Biomolecular and Biomedical Engineering School of Chemical Engineering and Technology Tianjin University Tianjin 300350 P. R. ChinaBeijing Institute of Microbiology and Epidemiology Beijing 100850 P. R. ChinaBeijing Institute of Microbiology and Epidemiology Beijing 100850 P. R. ChinaFrontiers Science Center for Synthetic Biology Key Laboratory of Systems Bioengineering (MOE) Institute of Biomolecular and Biomedical Engineering School of Chemical Engineering and Technology Tianjin University Tianjin 300350 P. R. ChinaBeijing Institute of Microbiology and Epidemiology Beijing 100850 P. R. ChinaFrontiers Science Center for Synthetic Biology Key Laboratory of Systems Bioengineering (MOE) Institute of Biomolecular and Biomedical Engineering School of Chemical Engineering and Technology Tianjin University Tianjin 300350 P. R. ChinaAbstract The extreme instability of mRNA makes the practical application of mRNA‐based vaccines heavily rely on efficient delivery system and cold chain transportation. Herein, a DNA‐based nanomachine, which achieves programmed capture, long‐term storage without cryopreservation, and efficient delivery of mRNA in cells, is developed. The polythymidine acid (Poly‐T) functionalized poly(N‐isopropylacrylamide) (DNA‐PNIPAM) is synthesized and assembled as the central compartment of the nanomachine. The DNA‐PNIPAM nano‐assembly exhibits reversible thermal‐responsive dynamic property: when lower than the low critical solution temperature (LCST, ≈32 °C) of PNIPAM, the DNA‐PNIPAM transforms into extension state to expose the poly‐T, facilitating the hybridization with polyadenylic acid (Poly‐A) tail of mRNA; when higher than LCST, DNA‐PNIPAM re‐assembles and achieves an efficient encapsulation of mRNA. It is remarkable that the DNA‐PNIPAM nano‐assembly realizes long‐term storage of mRNA (≈7 days) at 37 °C. Biodegradable 2‐hydroxypropyltrimethyl ammonium chloride chitosan is assembled on the outside of DNA‐PNIPAM to facilitate the endocytosis of mRNA, RNase‐H mediating mRNA release occurs in cytoplasm, and efficient mRNA translation is achieved. This work provides a new disign principle of nanosystem for mRNA delivery.https://doi.org/10.1002/advs.202204905DNA nanotechnologymRNA deliverynanomedicineself‐assembly |
| spellingShingle | Feng Li Xiaolei Sun Jing Yang Jin Ren Mengxue Huang Shengqi Wang Dayong Yang A Thermal and Enzymatic Dual‐Stimuli Responsive DNA‐Based Nanomachine for Controlled mRNA Delivery Advanced Science DNA nanotechnology mRNA delivery nanomedicine self‐assembly |
| title | A Thermal and Enzymatic Dual‐Stimuli Responsive DNA‐Based Nanomachine for Controlled mRNA Delivery |
| title_full | A Thermal and Enzymatic Dual‐Stimuli Responsive DNA‐Based Nanomachine for Controlled mRNA Delivery |
| title_fullStr | A Thermal and Enzymatic Dual‐Stimuli Responsive DNA‐Based Nanomachine for Controlled mRNA Delivery |
| title_full_unstemmed | A Thermal and Enzymatic Dual‐Stimuli Responsive DNA‐Based Nanomachine for Controlled mRNA Delivery |
| title_short | A Thermal and Enzymatic Dual‐Stimuli Responsive DNA‐Based Nanomachine for Controlled mRNA Delivery |
| title_sort | thermal and enzymatic dual stimuli responsive dna based nanomachine for controlled mrna delivery |
| topic | DNA nanotechnology mRNA delivery nanomedicine self‐assembly |
| url | https://doi.org/10.1002/advs.202204905 |
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