Abstract
mRNA therapies have emerged as a transformative class of medicines, offering immense potential across a diverse array of applications. This progress has been particularly evident in the wake of the success of lipid nanoparticle (LNP)-based mRNA vaccines during the COVID-19 pandemic. As these applications expand, the demand for sustained protein production has become increasingly critical. However, conventional mRNA therapies face significant challenges, including inherent RNA instability and suboptimal expression efficiency, often requiring repeated dosing to maintain therapeutic efficacy over time. This review highlights recent advances in strategies to prolong the therapeutic efficacy of LNP-mRNA systems. We focus on preclinical and emerging approaches aimed at extending the period of protein translation by engineering both the mRNA molecule and the LNP delivery system. Sustained protein expression is a cornerstone of mRNA-based therapeutics, and addressing this challenge is vital for unlocking their therapeutic potential. We hope this review provides valuable insights to guide the development of optimized delivery platforms for LNP-mRNA therapeutics.