Immunostimulatory Effects of Guanine-Quadruplex Topologies as Scaffolds for CpG Oligodeoxynucleotides
Synthetic cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODNs) are promising candidates for vaccine adjuvants, because they activate immune responses through the Toll-like receptor 9 (TLR9) pathway. However, unmodified CpG ODNs are quickly degraded by serum nucleases, and their negative charg...
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2025-01-01
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| author | Soumitra Pathak Nguyen Bui Thao Le Taiji Oyama Yusuke Odahara Atsuya Momotake Kazunori Ikebukuro Chiho Kataoka-Hamai Chiaki Yoshikawa Kohsaku Kawakami Yoshihisa Kaizuka Tomohiko Yamazaki |
| author_facet | Soumitra Pathak Nguyen Bui Thao Le Taiji Oyama Yusuke Odahara Atsuya Momotake Kazunori Ikebukuro Chiho Kataoka-Hamai Chiaki Yoshikawa Kohsaku Kawakami Yoshihisa Kaizuka Tomohiko Yamazaki |
| author_sort | Soumitra Pathak |
| collection | DOAJ |
| description | Synthetic cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODNs) are promising candidates for vaccine adjuvants, because they activate immune responses through the Toll-like receptor 9 (TLR9) pathway. However, unmodified CpG ODNs are quickly degraded by serum nucleases, and their negative charge hinders cellular uptake, limiting their clinical application. Our group previously reported that guanine-quadruplex (G4)-forming CpG ODNs exhibit enhanced stability and cellular uptake. G4 structures can form in parallel, anti-parallel, or hybrid topologies, depending on strand orientation, but the effects of these topologies on CpG ODNs have not yet been explored. In this study, we designed three distinct G4 topologies as scaffolds for CpG ODNs. Among the three topology, the parallel G4 CpG ODN demonstrated the highest serum stability and cellular uptake, resulting in the strongest immune response from macrophage cells. Additionally, we investigated the binding affinities of the different G4 topologies to macrophage scavenger receptor-1 and TLR9, both of which are key to immune activation. These findings provide valuable insights into the development of CpG ODN-based vaccine adjuvants. |
| format | Article |
| id | doaj-art-b47f6449ba72455db751c718fb7a556b |
| institution | Kabale University |
| issn | 2218-273X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj-art-b47f6449ba72455db751c718fb7a556b2025-01-24T13:25:09ZengMDPI AGBiomolecules2218-273X2025-01-011519510.3390/biom15010095Immunostimulatory Effects of Guanine-Quadruplex Topologies as Scaffolds for CpG OligodeoxynucleotidesSoumitra Pathak0Nguyen Bui Thao Le1Taiji Oyama2Yusuke Odahara3Atsuya Momotake4Kazunori Ikebukuro5Chiho Kataoka-Hamai6Chiaki Yoshikawa7Kohsaku Kawakami8Yoshihisa Kaizuka9Tomohiko Yamazaki10Research Center for Macromolecules and Biomaterials, National Institute for Materials Science (NIMS), 1-2-1 Sengen, Tsukuba 305-0047, JapanResearch Center for Macromolecules and Biomaterials, National Institute for Materials Science (NIMS), 1-2-1 Sengen, Tsukuba 305-0047, JapanJASCO Corporation, Hachioji 192-8537, JapanDepartment of Chemistry, University of Tsukuba, Tsukuba 305-8571, JapanDepartment of Chemistry, University of Tsukuba, Tsukuba 305-8571, JapanDepartment of Biotechnology and Life Science, Graduate School of Engineering, Tokyo University of Agriculture and Technology, Koganei 184-8588, JapanResearch Center for Macromolecules and Biomaterials, National Institute for Materials Science (NIMS), 1-2-1 Sengen, Tsukuba 305-0047, JapanResearch Center for Macromolecules and Biomaterials, National Institute for Materials Science (NIMS), 1-2-1 Sengen, Tsukuba 305-0047, JapanResearch Center for Macromolecules and Biomaterials, National Institute for Materials Science (NIMS), 1-2-1 Sengen, Tsukuba 305-0047, JapanResearch Center for Macromolecules and Biomaterials, National Institute for Materials Science (NIMS), 1-2-1 Sengen, Tsukuba 305-0047, JapanResearch Center for Macromolecules and Biomaterials, National Institute for Materials Science (NIMS), 1-2-1 Sengen, Tsukuba 305-0047, JapanSynthetic cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODNs) are promising candidates for vaccine adjuvants, because they activate immune responses through the Toll-like receptor 9 (TLR9) pathway. However, unmodified CpG ODNs are quickly degraded by serum nucleases, and their negative charge hinders cellular uptake, limiting their clinical application. Our group previously reported that guanine-quadruplex (G4)-forming CpG ODNs exhibit enhanced stability and cellular uptake. G4 structures can form in parallel, anti-parallel, or hybrid topologies, depending on strand orientation, but the effects of these topologies on CpG ODNs have not yet been explored. In this study, we designed three distinct G4 topologies as scaffolds for CpG ODNs. Among the three topology, the parallel G4 CpG ODN demonstrated the highest serum stability and cellular uptake, resulting in the strongest immune response from macrophage cells. Additionally, we investigated the binding affinities of the different G4 topologies to macrophage scavenger receptor-1 and TLR9, both of which are key to immune activation. These findings provide valuable insights into the development of CpG ODN-based vaccine adjuvants.https://www.mdpi.com/2218-273X/15/1/95CpG oligodeoxynucleotidesadjuvantsguanine-quadrupleximmune responsetoll like receptor 9macrophage cells |
| spellingShingle | Soumitra Pathak Nguyen Bui Thao Le Taiji Oyama Yusuke Odahara Atsuya Momotake Kazunori Ikebukuro Chiho Kataoka-Hamai Chiaki Yoshikawa Kohsaku Kawakami Yoshihisa Kaizuka Tomohiko Yamazaki Immunostimulatory Effects of Guanine-Quadruplex Topologies as Scaffolds for CpG Oligodeoxynucleotides Biomolecules CpG oligodeoxynucleotides adjuvants guanine-quadruplex immune response toll like receptor 9 macrophage cells |
| title | Immunostimulatory Effects of Guanine-Quadruplex Topologies as Scaffolds for CpG Oligodeoxynucleotides |
| title_full | Immunostimulatory Effects of Guanine-Quadruplex Topologies as Scaffolds for CpG Oligodeoxynucleotides |
| title_fullStr | Immunostimulatory Effects of Guanine-Quadruplex Topologies as Scaffolds for CpG Oligodeoxynucleotides |
| title_full_unstemmed | Immunostimulatory Effects of Guanine-Quadruplex Topologies as Scaffolds for CpG Oligodeoxynucleotides |
| title_short | Immunostimulatory Effects of Guanine-Quadruplex Topologies as Scaffolds for CpG Oligodeoxynucleotides |
| title_sort | immunostimulatory effects of guanine quadruplex topologies as scaffolds for cpg oligodeoxynucleotides |
| topic | CpG oligodeoxynucleotides adjuvants guanine-quadruplex immune response toll like receptor 9 macrophage cells |
| url | https://www.mdpi.com/2218-273X/15/1/95 |
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