Combined hybrid structure of siRNA tailed IVT mRNA (ChriST mRNA) for enhancing DC maturation and subsequent anticancer T cell immunity
- 주제(키워드) Cancer immunotherapy , Multifunctional RNA structure , siRNA , Synthetic mRNA
- 등재 SCIE, SCOPUS
- 발행기관 Elsevier B.V.
- 발행년도 2020
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000172287
- 본문언어 영어
- Published As https://dx.doi.org/10.1016/j.jconrel.2020.08.009
- PubMed https://pubmed.ncbi.nlm.nih.gov/32791078
- 저작권 이화여자대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
RNA therapeutics have received much attention in the development of anti-cancer therapies. Among them, synthetic mRNA (IVT mRNA) was investigated for cancer immunotherapy due to its abilities to express tumor associated antigens with stimulation of immune responses in dendritic cells (DCs). Despite of its great potential, several hurdles were remained such as insufficient immune stimulation and DC maturation. In this study, we aimed to present a novel IVT mRNA that can simultaneously express tumor associated antigens while suppress STAT3 proteins. Combined functions of siRNA and IVT mRNA were investigated and the hybrid structure of siRNA tailed mRNA (ChriST mRNA) was developed. We prepared the ChriST mRNA by employing polyA tail structures with RNAi sequences at the 3′ end of mRNA. Complementary strands were annealed to form duplex siRNA structure to induce STAT3 gene silencing. In addition, a hybrid structure of DNA/RNA was introduced into the ChriST mRNA between polyA tail and RNAi sequences. It was expected that DNA/RNA duplex would be readily cleaved by RNase H in the intracellular environment. After the cleavage, ChriST mRNA was fully functionalized in cells and exhibited enhanced tumor specific DC maturation. © 2020 Elsevier B.V.
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