Nanoprecipitation- and nanoemulsification-based systems for efficient nucleic acid delivery

Nanosystems are essential for ensuring protection, stability and efficient delivery of nucleic acids (NAs) across biological barriers, unlocking a new era of medicinal potentials. Messenger RNA (mRNA), small interfering RNA (siRNA), microRNA (miRNA) and plasmid DNA (pDNA), among others, have notably been explored as therapeutics in combination with nanoscale systems in applications such as vaccination and gene silencing. Over the years, a plethora of colloidal systems has been developed through diverse formulation approaches with nanoprecipitation and nanoemulsification emerging as efficient and scalable strategies able to tune and control the physicochemical properties of the produced nanocarriers. In the present review we highlight recent progress in nanoprecipitation and nanoemulsification approaches for the development of nanosystems with genetic cargo, discussing their principles, formulation parameters, and their application across different carrier systems including lipid nanoparticles (LNPs), liposomes, polymeric nanoparticles (PNPs), hybrid structures and nanoemulsions (NEs). Composition, encapsulation efficiency (EE), and biological performance along with scalability and clinical translation are examined as they are shaping next-generation platforms for NA therapeutics, offering opportunities to refine delivery efficiency, reduce toxicity, and broaden clinical translation ultimately increasing patient access to advanced therapies.