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Nanoparticles / Lipid Nanoparticles / Cell- and Tissue-based Therapy · Journal article
Drug Delivery · August 12, 2026
A consensus or society position rather than new primary data.
This is a comprehensive review of engineering strategies for targeted mRNA delivery to immune cells in vivo, focusing on lipid nanoparticle design, biological barriers, and translational applications in oncology and autoimmunity. The work frames in vivo immune cell programming as an emerging paradigm shift from ex vivo CAR-T manufacturing, identifying key technical hurdles and material science advances needed for clinical translation.
Review Article. Patients requiring immune cell engineering therapies; focus on oncology, autoimmune disease, protein replacement, and tissue regeneration applications. Guangzhou, China (author affiliations).
mRNA vaccines deployed during COVID-19 validated safety and scalability of mRNA-based therapeutics and nonviral delivery platforms Conventional ex vivo CAR-T cell therapy requires extended manufacturing durations (typically 3–4 weeks), high costs, and necessitates lymphodepletion before infusion, increasing infection risk In vivo CAR-T generation eliminates the need for lymphodepletion and reduces risks associated with ex vivo cell expansion and reinfusion
Specific efficacy metrics, safety outcomes, and comparator data from clinical trials are not presented in this excerpt mRNA vaccines deployed during COVID-19 validated safety and scalability of mRNA-based therapeutics and nonviral delivery platforms
Clinicians and translational researchers should recognize the paradigm shift from ex vivo to in vivo immune cell engineering as a potential approach to reduce manufacturing complexity, cost, and patient morbidity, while understanding that efficient targeted mRNA delivery to specific immune cell subsets remains a major translational hurdle. The review identifies rational material design, high-throughput screening, and artificial intelligence integration as critical next steps toward clinical translation.
A comprehensive review article synthesizing current knowledge on mRNA delivery engineering strategies to immune cells, identifying translational barriers and technical advances rather than reporting original experimental results or clinical outcomes.
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Clinicians and translational researchers should recognize the paradigm shift from ex vivo to in vivo immune cell engineering as a potential approach to reduce manufacturing complexity, cost, and patient morbidity, while understanding that efficient targeted mRNA delivery to specific immune cell subsets remains a major translational hurdle. The review identifies rational material design, high-throughput screening, and artificial intelligence integration as critical next steps toward clinical translation.
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Messenger RNA (mRNA) therapeutics have revolutionized biomedicine by enabling direct in vivo programming of immune cells. This strategy bypasses the complex manufacturing and high costs associated with ex vivo cell therapies. However, efficient and specific systemic delivery of mRNA to target immune cell subsets remains a major translational hurdle. This review systematically examines engineering strategies that address this challenge. We first outline the key biological barriers to mRNA delivery, such as serum instability, nonspecific biodistribution, cellular uptake heterogeneity, and inefficient endosomal escape. Next, we comprehensively review advances in lipid nanoparticle (LNP) engineering, including discovering novel lipids, modulating compositions, conjugating targeting ligands, and incorporating stimuli-responsive elements, to enable enhanced tropism toward specific immune cells. Representative applications in oncology, protein replacement, autoimmune disease, and tissue regeneration are highlighted. Finally, we address translational challenges in safety, scalable manufacturing, and regulatory issues. The integration of rational material design, high-throughput screening, artificial intelligence, and interdisciplinary collaboration will be essential to advance next-generation targeted in vivo mRNA cell therapies toward clinical translation.
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