Strategies for controlled assembly of rod-shaped viral particles

Abstract

Nanoparticles are increasingly used in medical applications due to their precise control over size, shape, and surface properties, which enable safe, targeted delivery and controlled interactions with specific tissues and cell types, ultimately enhancing therapeutic outcomes. While synthetic nanoparticles have shown promise, they often face challenges related to toxicity, biocompatibility, and uniformity. In contrast, naturally derived particles offer inherent advantages, including biological compatibility and monodispersity, which help mitigate these issues. Rod-shaped viruses and virus-like particles (VLPs) are particularly attractive due to their directional assembly into hierarchical structures, uniform size, ease of surface functionalization, and tunable aspect ratio. These properties are useful to control biodistribution and cellular interactions for nanoparticle accumulation and targeted delivery in vivo. Ongoing efforts to harness rod-shaped virus-like particles for nanomedicine involve a variety of strategies to control assembly, such as genetic changes to coat proteins, RNA scaffold engineering, and physicochemical changes to the solution conditions. These strategies enable precise tuning of VLP shape, aspect ratio, and composition. This review summarizes available assembly strategies and highlights their impact on particle morphology. Limitations of current strategies and opportunities for implementing the currently known assembly techniques in nanomedicine are also discussed.