Virus-like particles based on plant viruses and bacteriophages: emerging strategies for the delivery of nucleic acid therapeutics.

Nucleic acids have emerged as a robust modality for the treatment of various diseases that are considered undruggable in the context of small-molecule therapeutics. However, their clinical translation is hindered by the lack of safe and effective delivery across extracellular and intracellular barriers. Mammalian viral vectors and synthetic non-viral carriers have long dominated the delivery landscape, but these raise concerns about safety and immunogenicity, driving the search for alternative strategies. Recently, non-mammalian viral vectors (based on plant viruses or bacteriophages) and virus-like particles (VLPs) derived from them have gained attention as bioinspired platforms for nucleic acid drug delivery. Their well-defined architecture, scalable production, and ability to encapsulate or display drug cargoes offer versatility for drug delivery. This review highlights recent progress in the engineering of plant viruses and bacteriophages for nucleic acid delivery, emphasizing their potential as non-infectious viral scaffolds for next-generation therapeutic platforms.