Approach To Treatment-Resistant Recurrent Depressive Disorder.

Lipid nanoparticle (LNP)–encapsulated messenger RNA (mRNA) has emerged as a versatile therapeutic modality for protein expression. [] A typical synthetic mRNA consists of a 5’ cap, untranslated regions, an open reading frame, and a poly(A) tail, with extensive optimization strategies employed to enhance stability and modulate innate immune activation. [] These efforts include chemical nucleoside modifications, advanced purification methods, and rational sequence design. [] LNPs, composed of ionizable lipids, phospholipids, cholesterol, and polyethylene glycol (PEG)-lipids, protect mRNA from degradation and enable intracellular delivery, while also influencing biodistribution, immune recognition, and transfection efficiency. Together, mRNA design and LNP formulation define the safety, efficacy, and translational performance of this new modality. [–] Key advantages of mRNA–LNP platforms include fast modular design, rapid manufacturing, and scalable production. The COVID-19 pandemic provided a real-world demonstration of these capabilities, with first-generation SARS-CoV-2 vaccines progressing from sequence identification to phase I clinical testing within months. [] Nowadays mRNA–LNP technologies have rapidly transitioned from experimental tools to clinically viable drug platforms with growing regulatory and commercial momentum. Beyond COVID-19, mRNA–LNP therapeutics are being actively explored for a wide range of infectious diseases and oncology applications, with multiple candidates showing promising preclinical and early clinical outcomes. [, ] In cancer immunotherapy, development has increasingly shifted from dendritic cell–based approaches toward LNP-mediated mRNA delivery, offering improved scalability and manufacturing simplicity. [] In parallel, targeted LNP strategies have enabled cell engineering, including selective delivery of chimeric antigen receptor (CAR) mRNA to T cell subsets, highlighting the potential of mRNA–LNPs to expand access to cellular immunotherapies. [] Many mRNA-LNP therapeutics are currently under development because of their unique advantages. A review identified 84 ongoing mRNA therapeutic trials, including 46 lipid-carrier-based mRNA therapeutic trials as of August 2023. [] However, the broader translation of mRNA-LNP therapeutics remains challenging and has shown relatively low success rates. For example, a 2025 -based analysis reported 238 global mRNA clinical programs, but only 34% had advanced beyond Phase I.[] This low rate of successful clinical translation shows the substantial challenges associated with advancing mRNA–LNP technologies from preclinical animal models to human applications.