Poly(ethylene Glycol) (PEG)–OligoRNA Hybridization to mRNA Enables Fine‐Tuned Polyplex PEGylation for Spleen‐Targeted mRNA Delivery
Organ‐selective targeting of mRNA polyplexes has been rarely explored despite the substantial potential of polymer‐based systems in mRNA delivery. In this study, spleen‐selective delivery of polyplexes is achieved by employing mRNA engineering to coat them with poly(ethylene glycol) (PEG). In this a...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley-VCH
2024-04-01
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| Series: | Small Science |
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| Online Access: | https://doi.org/10.1002/smsc.202300258 |
| _version_ | 1797205948588097536 |
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| author | Miki Suzuki Yuki Mochida Mao Hori Akimasa Hayashi Kazuko Toh Theofilus A. Tockary Xueying Liu Victor Marx Hidetomo Yokoo Kanjiro Miyata Makoto Oba Satoshi Uchida |
| author_facet | Miki Suzuki Yuki Mochida Mao Hori Akimasa Hayashi Kazuko Toh Theofilus A. Tockary Xueying Liu Victor Marx Hidetomo Yokoo Kanjiro Miyata Makoto Oba Satoshi Uchida |
| author_sort | Miki Suzuki |
| collection | DOAJ |
| description | Organ‐selective targeting of mRNA polyplexes has been rarely explored despite the substantial potential of polymer‐based systems in mRNA delivery. In this study, spleen‐selective delivery of polyplexes is achieved by employing mRNA engineering to coat them with poly(ethylene glycol) (PEG). In this approach, mRNA is hybridized with PEGylated complementary RNA oligonucleotides (PEG–OligoRNAs), followed by the addition of linear poly(ethyleneimine). In this method, it is ensured that nearly all added PEG strands bind to the polyplexes, thereby enabling precise control of PEG amounts on the surface. Following systemic injection into mice, non‐PEGylated polyplexes yield robust protein expression in the lung and spleen. Intriguingly, adding a small number of PEG–OligoRNAs drastically reduces protein expression efficiency in the lung while preserving it in the spleen, realizing spleen targeting of mRNA polyplexes. Furthermore, PEGylated polyplexes demonstrate their potential utility in mRNA vaccination. In mechanistic analyses, non‐PEGylated polyplexes immediately agglomerate in the blood and deposit in the lung. Coating polyplexes with a small amount of short PEG effectively prevents these processes. Notably, even slight changes in PEG amounts and lengths dramatically impact the physicochemical properties and biological functionalities of the polyplexes, emphasizing the benefits of an mRNA engineering‐based approach for fine‐tuning polyplex PEG coating. |
| first_indexed | 2024-04-24T08:59:14Z |
| format | Article |
| id | doaj.art-fe7bde1132c74192b0fb44db21d9b503 |
| institution | Directory Open Access Journal |
| issn | 2688-4046 |
| language | English |
| last_indexed | 2024-04-24T08:59:14Z |
| publishDate | 2024-04-01 |
| publisher | Wiley-VCH |
| record_format | Article |
| series | Small Science |
| spelling | doaj.art-fe7bde1132c74192b0fb44db21d9b5032024-04-16T04:15:54ZengWiley-VCHSmall Science2688-40462024-04-0144n/an/a10.1002/smsc.202300258Poly(ethylene Glycol) (PEG)–OligoRNA Hybridization to mRNA Enables Fine‐Tuned Polyplex PEGylation for Spleen‐Targeted mRNA DeliveryMiki Suzuki0Yuki Mochida1Mao Hori2Akimasa Hayashi3Kazuko Toh4Theofilus A. Tockary5Xueying Liu6Victor Marx7Hidetomo Yokoo8Kanjiro Miyata9Makoto Oba10Satoshi Uchida11Medical Chemistry Graduate School of Medical Science Kyoto Prefectural University of Medicine 1‐5 Shimogamohangi‐cho, Sakyo‐ku Kyoto 606‐0823 JapanDepartment of Advanced Nanomedical Engineering Medical Research Institute Tokyo Medical and Dental University (TMDU) 1‐5‐45 Yushima, Bunkyo‐ku Tokyo 113‐8510 JapanDepartment of Materials Engineering Graduate School of Engineering The University of Tokyo 7‐3‐1 Hongo, Bunkyo‐ku Tokyo 113‐8656 JapanDepartment of Pathology Kyorin University School of Medicine 6‐20‐2 Shinkawa, Mitaka‐shi Tokyo 181‐8611 JapanInnovation Center of NanoMedicine (iCONM) Kawasaki Institute of Industrial Promotion 3‐25‐14 Tonomachi, Kawasaki‐ku Kawasaki 210‐0821 JapanInnovation Center of NanoMedicine (iCONM) Kawasaki Institute of Industrial Promotion 3‐25‐14 Tonomachi, Kawasaki‐ku Kawasaki 210‐0821 JapanInnovation Center of NanoMedicine (iCONM) Kawasaki Institute of Industrial Promotion 3‐25‐14 Tonomachi, Kawasaki‐ku Kawasaki 210‐0821 JapanMedical Chemistry Graduate School of Medical Science Kyoto Prefectural University of Medicine 1‐5 Shimogamohangi‐cho, Sakyo‐ku Kyoto 606‐0823 JapanMedical Chemistry Graduate School of Medical Science Kyoto Prefectural University of Medicine 1‐5 Shimogamohangi‐cho, Sakyo‐ku Kyoto 606‐0823 JapanDepartment of Materials Engineering Graduate School of Engineering The University of Tokyo 7‐3‐1 Hongo, Bunkyo‐ku Tokyo 113‐8656 JapanMedical Chemistry Graduate School of Medical Science Kyoto Prefectural University of Medicine 1‐5 Shimogamohangi‐cho, Sakyo‐ku Kyoto 606‐0823 JapanMedical Chemistry Graduate School of Medical Science Kyoto Prefectural University of Medicine 1‐5 Shimogamohangi‐cho, Sakyo‐ku Kyoto 606‐0823 JapanOrgan‐selective targeting of mRNA polyplexes has been rarely explored despite the substantial potential of polymer‐based systems in mRNA delivery. In this study, spleen‐selective delivery of polyplexes is achieved by employing mRNA engineering to coat them with poly(ethylene glycol) (PEG). In this approach, mRNA is hybridized with PEGylated complementary RNA oligonucleotides (PEG–OligoRNAs), followed by the addition of linear poly(ethyleneimine). In this method, it is ensured that nearly all added PEG strands bind to the polyplexes, thereby enabling precise control of PEG amounts on the surface. Following systemic injection into mice, non‐PEGylated polyplexes yield robust protein expression in the lung and spleen. Intriguingly, adding a small number of PEG–OligoRNAs drastically reduces protein expression efficiency in the lung while preserving it in the spleen, realizing spleen targeting of mRNA polyplexes. Furthermore, PEGylated polyplexes demonstrate their potential utility in mRNA vaccination. In mechanistic analyses, non‐PEGylated polyplexes immediately agglomerate in the blood and deposit in the lung. Coating polyplexes with a small amount of short PEG effectively prevents these processes. Notably, even slight changes in PEG amounts and lengths dramatically impact the physicochemical properties and biological functionalities of the polyplexes, emphasizing the benefits of an mRNA engineering‐based approach for fine‐tuning polyplex PEG coating.https://doi.org/10.1002/smsc.202300258intravital imagingsmRNA deliveriesmRNA engineeringspolyplexestissue targetings |
| spellingShingle | Miki Suzuki Yuki Mochida Mao Hori Akimasa Hayashi Kazuko Toh Theofilus A. Tockary Xueying Liu Victor Marx Hidetomo Yokoo Kanjiro Miyata Makoto Oba Satoshi Uchida Poly(ethylene Glycol) (PEG)–OligoRNA Hybridization to mRNA Enables Fine‐Tuned Polyplex PEGylation for Spleen‐Targeted mRNA Delivery Small Science intravital imagings mRNA deliveries mRNA engineerings polyplexes tissue targetings |
| title | Poly(ethylene Glycol) (PEG)–OligoRNA Hybridization to mRNA Enables Fine‐Tuned Polyplex PEGylation for Spleen‐Targeted mRNA Delivery |
| title_full | Poly(ethylene Glycol) (PEG)–OligoRNA Hybridization to mRNA Enables Fine‐Tuned Polyplex PEGylation for Spleen‐Targeted mRNA Delivery |
| title_fullStr | Poly(ethylene Glycol) (PEG)–OligoRNA Hybridization to mRNA Enables Fine‐Tuned Polyplex PEGylation for Spleen‐Targeted mRNA Delivery |
| title_full_unstemmed | Poly(ethylene Glycol) (PEG)–OligoRNA Hybridization to mRNA Enables Fine‐Tuned Polyplex PEGylation for Spleen‐Targeted mRNA Delivery |
| title_short | Poly(ethylene Glycol) (PEG)–OligoRNA Hybridization to mRNA Enables Fine‐Tuned Polyplex PEGylation for Spleen‐Targeted mRNA Delivery |
| title_sort | poly ethylene glycol peg oligorna hybridization to mrna enables fine tuned polyplex pegylation for spleen targeted mrna delivery |
| topic | intravital imagings mRNA deliveries mRNA engineerings polyplexes tissue targetings |
| url | https://doi.org/10.1002/smsc.202300258 |
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