Circular RNA vaccine induces potent T cell responses
Year: 2023
Type: article
Abstract: Circular RNAs (circRNAs) are a class of RNAs commonly found across eukaryotes and viruses, characterized by their resistance to exonuclease-mediated degradation. Their superior stability compared to linear RNAs, combined with previous work showing that engineered circRNAs serve as efficient protein translation templates, make circRNA a promising candidate for RNA medicine. Here, we systematically examine the adjuvant activity, route of administration, and antigen-specific immunity of circRNA vaccination in mice. Potent circRNA adjuvant activity is associated with RNA uptake and activation of myeloid cells in the draining lymph nodes and transient cytokine release. Immunization of mice with engineered circRNA encoding a protein antigen delivered by a charge-altering releasable transporter induced innate activation of dendritic cells, robust antigen-specific CD8 T cell responses in lymph nodes and tissues, and strong antitumor efficacy as a therapeutic cancer vaccine. These results highlight the potential utility of circRNA vaccines for stimulating potent innate and T cell responses in tissues.
Language: English
Topic: Circular RNAs in diseases
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Awards: G1464935199, New Materials to Deliver mRNA: Applications in Cancer Immunotherapy, G2657829865, G347281353, System Biological Analyses of Innate and Adaptive Responses to Vaccination, G619242983, G682414912, Microbes, Dendritic Cell Subsets and T-Cell Immunity, Metabolic imprinting of dendritic cell fate and function in tissues, G9000006652, G9000020761, G9000051380, G9000125926, Vaccine and Infection Induced Immunity in the Young and Aged, Understanding the Role of Mucosal Antigen Presenting Cells in Regulating Immune Response
OpenAlex ID: W4375954875