Circular RNA vaccine induces potent T cell responses.
Circular RNA vaccine induces potent T cell responses.
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DOI：
10.1073/pnas.2302191120
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发表时间：
2023-05-16
影响因子：
11.1
通讯作者：
Chang, Howard Y.
中科院分区：
文献类型：
--
作者：
Amaya, Laura;Grigoryan, Lilit;Li, Zhijian;Lee, Audrey;Wender, Paul A.;Pulendran, Bali;Chang, Howard Y.
环状rna （circRNAs）是一类独特的rna，与线性mrna相比具有高度稳定性，可以通过工程设计提供持久的蛋白质表达。该研究表明，通过改变电荷的可释放转运体传递的编码抗原蛋白序列的circRNA可以有效地作为佐剂和免疫原，诱导有效的细胞免疫并导致肿瘤清除，当用作治疗性疫苗时。这些结果表明，经过改造的环状rna可用于开发疫苗和治疗方法。环状rna （circRNAs）是一类常见于真核生物和病毒的rna，其特点是它们对外切酶介导的降解具有抗性。与线性RNA相比，它们具有优越的稳定性，结合先前的研究表明，工程circRNA可以作为有效的蛋白质翻译模板，使circRNA成为RNA医学的有希望的候选者。在这里，我们系统地研究了小鼠circRNA疫苗的佐剂活性、给药途径和抗原特异性免疫。有效的环状RNA佐剂活性与引流淋巴结中髓细胞的RNA摄取和激活以及短暂的细胞因子释放有关。编码一种由改变电荷的可释放转运体递送的蛋白抗原的工程化circRNA免疫小鼠，诱导树突状细胞的先天活化，在淋巴结和组织中产生强大的抗原特异性CD8 T细胞反应，并作为治疗性癌症疫苗具有很强的抗肿瘤功效。这些结果强调了circRNA疫苗在刺激组织中有效的先天和T细胞反应方面的潜在效用。
Circular RNAs (circRNAs) are a unique class of RNAs that are highly stable compared to linear mRNAs and can be engineered to provide durable protein expression. This study demonstrates that circRNA encoding antigenic protein sequences delivered by a charge-altering releasable transporter can effectively serve as both an adjuvant and an immunogen, inducing potent cellular immunity and leading to tumor clearance when used as a therapeutic vaccine. These results suggest engineered circRNAs for the development of vaccines and therapeutics. 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.
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影响因子：
3.7
作者：
Lasda E;Parker R
通讯作者：
Parker R
影响因子：
46.9
作者：
Chen R;Wang SK;Belk JA;Amaya L;Li Z;Cardenas A;Abe BT;Chen CK;Wender PA;Chang HY
通讯作者：
Chang HY
影响因子：
16
作者：
Chen, Y. Grace;Chen, Robert;Chang, Howard Y.
通讯作者：
Chang, Howard Y.
DOI：
10.1016/j.omtn.2021.01.003
发表时间：
2021-03-05
期刊：
Molecular therapy. Nucleic acids
影响因子：
--
作者：
Meganck RM;Liu J;Hale AE;Simon KE;Fanous MM;Vincent HA;Wilusz JE;Moorman NJ;Marzluff WF;Asokan A
通讯作者：
Asokan A
影响因子：
18.2
作者：
Haabeth OAW;Lohmeyer JJK;Sallets A;Blake TR;Sagiv-Barfi I;Czerwinski DK;McCarthy B;Powell AE;Wender PA;Waymouth RM;Levy R
通讯作者：
Levy R