POS8-0913

Designing Affine Poly(A) tails for Vector Stabilization and Protein Expression

Topic

S8. Frontiers of Functional Polymers in Biology and Medicine

When and Where

Oct 1, 2026 08:30 - 09:30

Room 301 (Grand Ballroom)

Session Chairs

Jinkee HONG

Ki Su KIM

Presenter(s)

Jin Kim (Korea University)

Co-Author(s)

Minsa Park (College of Health Science, Korea University, Seoul, Republic of Korea), Sora Son (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinju, Gyeongsangnam-do, Republic of Korea), Hyunju Kim (Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea), Hye Seung Song (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinju, Gyeongsangnam-do, Republic of Korea), Young-suk Lee (Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea), Kyuri Lee (College of Health Science, Korea University, Seoul, Republic of Korea)

Abstract

The 3' end stretch of adenosine sequence also known as the poly(A) tail is one of the key determinants of the mRNA efficacy for therapeutics and vaccines. The poly(A) tail acts as a molecular barrier that protects the mRNA body from promiscuous degradation and is thus tightly regulated by multiple deadenylase complexes. However, engineering this structure at the 3' end of in vitro transcribed (IVT) mRNA in a scalable and consistent manner remains a challenge. Here, we present a sequence-design solution for poly(A) tails that overcomes these challenges in terms of vector stabilization and protein expression. Inspired by the activity of non-canonical poly(A) polymerases, we designed poly(A) tails with intermittent non-adenosines that follow an affine pattern of short adenosine sequences and one or two non-adenosines. As a result, we were able to construct plasmid vectors with poly(dA:dT) of up to 186 nts that are stable in E. coli even after reseeding. Further optimization of this affine design led to improved protein expression both in vitro and in vivo, thus extending the utility of mRNA-based medicine and its development.

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