Noble linear mRNA structures for prolonged protein expression
발표자
김은빈 (이화여자대학교)
연구책임자
이혁진 (서울대학교)
공동저자
김은빈 (이화여자대학교), 황유나 (이화여자대학교), 이혁진 (서울대학교)
초록
내용
mRNA is a promising platform for gene therapy and vaccine development, but its application is limited by instability caused by rapid decapping and deadenylation. To increase translation efficiency, we studied mRNA structures that minimize immunogenicity and improve stability. A chemically modified poly(A) tail was synthesized and evaluated for resistance to a cellular nuclease (CNOT7) and for binding affinity to poly(A)-binding protein (PABP). The modified tail was ligated to the 3′ end of an in vitro–transcribed GFP reporter mRNA, and its intracellular stability and expression were analyzed. The modified poly(A) tail showed increased resistance to nuclease-mediated degradation while maintaining comparable PABP binding. The IVT mRNA GFP reporter incorporating the modified poly(A) tail exhibited higher production yield and protein expression than conventional IVT mRNA. Application of the modified poly(A) tail to CD19-CAR-T mRNA increased CAR expression and enhanced cytotoxic activity.