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author：

Yu, H. (Yu, H..) [1] | Wen, Y. (Wen, Y..) [2] | Yu, W. (Yu, W..) [3] | Lu, L. (Lu, L..) [4] | Yang, Y. (Yang, Y..) [5] | Liu, C. (Liu, C..) [6] | Hu, Z. (Hu, Z..) [7] | Fang, Z. (Fang, Z..) [8] | Huang, S. (Huang, S..) [9]

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Scopus

Abstract：

Rationale:　Circular　RNA　(circRNA)　has　gained　attention　as　a　promising　platform　for　mRNA　vaccines　due　to　its　stability,　sustained　protein　expression,　and　intrinsic　immunostimulatory　properties.　This　study　aimed　to　design　and　optimize　a　circRNA　cancer　vaccine　platform　by　screening　for　efficient　internal　ribosome　entry　sites　(IRES)　and　enhancing　circRNA　translation　efficiency　for　improved　cancer　immunotherapy.　Methods:　We　screened　29　IRES　elements　to　identify　the　most　efficient　one　for　immune　cell　translation,　ultimately　discovering　the　Enterovirus　A　(EV-A)　IRES.　Using　SHAPE-MaP　technology,　we　analyzed　the　secondary　structure　of　circRNA　and　introduced　targeted　mutations　and　deletions　to　optimize　translation　efficiency.　Additionally,　we　investigated　the　regulatory　roles　of　spacer　sequences　and　microRNA　recognition　sites　in　circRNA　design　and　examined　the　mechanisms　behind　IRES-mediated　translation　initiation.　Results:　The　EV-A　IRES　was　identified　as　the　most　efficient　for　immune　cell　translation.　Structural　modifications　and　optimization　of　spacer　sequences　enhanced　the　translation　efficiency　of　circRNA.　Comparative　studies　demonstrated　that　circRNA　vaccines　induced　stronger　T　cell　immune　responses　and　exhibited　superior　tumor　prevention　and　therapeutic　efficacy　compared　to　traditional　linear　mRNA　vaccines.　Conclusion:　The　optimized　tumor　antigen　circRNA　vaccine　platform　offers　a　stable,　efficient　alternative　to　conventional　mRNA　vaccines　for　cancer　immunotherapy,　with　enhanced　immune　responses　and　improved　therapeutic　outcomes.　This　work　lays　the　foundation　for　developing　circRNA-based　vaccines　as　a　novel　strategy　for　cancer　treatment.　©　The　author(s).

Keyword：

Cancer vaccine Circular RNA Human papillomavirus (HPV) cancer vaccine Internal ribosome entry sites (IRES) Tumor neoantigen

Community：

  • [ 1 ] [Yu H.]Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
  • [ 2 ] [Yu H.]Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
  • [ 3 ] [Wen Y.]Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
  • [ 4 ] [Wen Y.]Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
  • [ 5 ] [Yu W.]Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
  • [ 6 ] [Yu W.]Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
  • [ 7 ] [Lu L.]Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
  • [ 8 ] [Lu L.]Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
  • [ 9 ] [Yang Y.]Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
  • [ 10 ] [Yang Y.]Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
  • [ 11 ] [Liu C.]Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
  • [ 12 ] [Liu C.]Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
  • [ 13 ] [Hu Z.]Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
  • [ 14 ] [Hu Z.]Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
  • [ 15 ] [Fang Z.]Department of Oncology and Vascular Interventional Therapy, Clinical Oncology School of Fujian Medical University, Fujian Key Laboratory of Translational Cancer Medicine, Fujian Cancer Hospital, Fujian Branch of Fudan University Shanghai Cancer Center, Fuzhou, 350014, China
  • [ 16 ] [Fang Z.]Department of Interventional Radiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Afliated Provincial Hospital, Fuzhou, 350001, China
  • [ 17 ] [Huang S.]Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
  • [ 18 ] [Huang S.]Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China

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Source ：

Theranostics

ISSN： 1838-7640

Year： 2025

Issue： 4

Volume： 15

Page： 1420-1438

1 2 . 4 0 0

JCR@2023

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ESI Highly Cited Papers on the List： 0 Unfold All

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