Lipid nanocarriers for RNA and DNA therapeutics: Next-generation delivery strategies in precision medicine

The COVID-19 pandemic has significantly accelerated the advancement of nucleic acid (NA) therapeutics, highlighting their transformative potential for treating diverse diseases with exceptional target specificity and pharmacological efficacy. Despite their promising therapeutic properties, NAs, including siRNA, miRNA, and mRNA, and DNA, face delivery challenges due to their inherent instability, polyanionic nature, and limited membrane permeability. In this review, we comprehensively evaluated lipid-based nanoparticle systems as leading solutions for NA delivery, examining various architectures such as cationic lipid nanoparticles, ionizable lipid nanoparticles (LNPs), solid lipid nanoparticles (SLNs), and lipid nanodiscs (LNDs). We highlight key findings demonstrating the pros and cons of each lipid nanosystem in overcoming heterogeneous delivery barriers, contending that rational engineering of these carriers can enhance overall delivery efficacy while enabling bespoke configurations for precision–targeted applications. Furthermore, based on the current knowledge discussed in this review, emerging perspectives on fine–tuning nanoparticle dimensions and systematically leveraging AI–driven optimization strategies for the rational design of next–generation, on–demand precision NA therapeutics are presented.