A newly published review in Medicine Plus provides as systematic evaluation of messenger RNA lipid nanoparticle (mRNA-LNP) technology, charting its evolution from prophylactic vaccines toward a versatile, programmable therapeutic platform. Led by Academician Yuzhang Wu and Prof. Jian Li from the Chongqing International Institute for Immunology and the Institute of Immunology at the Third Military Medical University (Army Medical University), the review distinguishes established clinical breakthroughs from emerging preclinical strategies across oncology, autoimmune disorders, rare genetic conditions, and tissue repair.
The authors emphasize that mRNA-LNPs are fundamentally shifting the paradigm of drug delivery. In this framework, mRNA acts as a transient molecular instruction while the LNP serves as a functional vehicle that governs cellular entry and bio-distribution. This universal framework now enables vaccines and mRNA-encoded antibodies, personalized cancer vaccines, antigen-specific immune tolerance induction, transient protein replacement and in vivo gene editing.
mRNA-LNPs provide a common delivery framework across infectious disease, oncology, autoimmunity, rare genetic disease and tissue repair. The lower panel highlights active extrahepatic targeting, AI-assisted sequence and UTR design, and longer-expression RNA formats.
A highlight of this platform evolution is the direct in vivo generation of CAR-engineered cells . As detailed in the review, targeted LNPs can deliver CAR-encoding mRNA directly to specific immune cells (such as T cells or macrophages) within the patient’s body. Once internalized, the mRNA is translated, displaying the functional CAR proteins on the cell surface to recognize and eliminate target cells. Compared with conventional ex vivo CAR-T manufacturing—which requires complex cell extraction, viral transduction, and extensive expansion— in vivo reprogramming offers a streamlined, off-the-shelf alternative that drastically reduces turnaround time and cost.
A targeted LNP carries CAR-encoding mRNA to a T cell. After cellular uptake and endosomal release, the mRNA is translated in the cytoplasm and CAR protein is displayed on the cell surface, creating a transient CAR-T cell that can recognize and kill target cells.
Despite these advances, the review highlights critical translational hurdles that must be overcome for broader clinical adoption:
Looking into the future, the review outlines next-generation strategies to address these challenges. These include high-throughput in vivo LNP screening, tissue- and cell-selective targeting, AI-assisted mRNA design, and advanced RNA formats—such as self-amplifying RNA (saRNA) and circular RNA (circRNA)—that extend expression kinetics. The authors conclude that therapeutic success will rely on carefully balancing dose, expression duration, immunogenicity, and manufacturability for each specific clinical indication.
Medicine Plus
Literature review