Nanotechnology and lipid-based nanoparticles for MRNA and gene therapy applications

Abstract

Nanotechnology has become a cornerstone of modern biotherapeutics, driving major advances in messenger RNA (mRNA) and gene therapy by enabling precise, efficient, and targeted intracellular delivery. Among the non-viral systems, lipid-based nanoparticles (LNPs) have achieved remarkable clinical relevance, most notably in mRNA vaccines and emerging gene-editing platforms. This review explores the integration of nanotechnology with lipid-based carrier systems in mRNA and gene-therapy applications. It provides an overview of lipid-based nanocarrier engineering encompassing liposomes, solid lipid nanoparticles, and ionizable lipid nanoparticles—alongside the mechanistic insights into LNP-mediated mRNA transport, including encapsulation, uptake, endosomal escape, and cytoplasmic release. Furthermore, we evaluate the newest developments in LNPs for gene-therapy applications beyond vaccination, such as protein replacement, long-term gene expression, and genome editing. Optimization strategies derived from nanotechnological innovations including surface engineering, organ-specific targeting, and improved formulation stability are examined, with an emphasis on translational safety, toxicity, and regulatory perspectives. Lastly, the review highlights ongoing challenges and future directions, such as immunogenicity mitigation, biodistribution control, scalable production, and standardization of clinical assessment. The intersection of nanotechnology and lipid-based delivery systems continues to shape the future of mRNA and gene therapy, expanding their therapeutic promise across diverse disease indications.