nonviral

Nonviral refers to methods for delivering genetic material or editing machinery that do not rely on viral vectors. In gene delivery and genome engineering, nonviral approaches aim to transfer DNA, RNA, or protein cargo into cells while avoiding the use of replication-competent viruses. Nonviral strategies are typically categorized into physical methods, chemical/nano-delivery systems, and nucleic acid–based approaches. Physical methods include electroporation, microinjection, sonoporation (using ultrasound), and magnetofection, which use external forces or fields to facilitate cellular uptake. Chemical approaches involve lipid- or polymer-based carriers, dendrimers, and inorganic nanoparticles such as gold or silica, often formulated as nanoparticles or complexes with the nucleic acid. Nucleic acid–based nonviral delivery includes direct delivery of mRNA, siRNA, or plasmid DNA, sometimes with chemical modifications to improve stability or targeting. Some nonviral systems are designed for ex vivo modification of cells, while others aim for in vivo delivery.

Advantages include lower immunogenicity and simpler manufacturing compared with viral vectors, reduced risk of insertional mutagenesis (though some nonviral methods may integrate at low frequency), and the ability to carry larger payloads. Disadvantages include lower transfection efficiency, transient expression, tissue targeting challenges, and potential toxicity.

Applications span basic research, vaccines (notably lipid nanoparticle–encapsulated mRNA in vaccines), gene therapy, and genome editing. Examples include lipid nanoparticle formulations for mRNA delivery, polymer-based carriers, and transposon-based systems such as Sleeping Beauty or piggyBac as nonviral methods for integrating genes. The clinical status is favorable for some vaccines and ex vivo editing approaches, with ongoing research to improve efficiency, targeting, and safety as regulatory landscapes evolve.