Design Strategies for Heterologous Molecule Display Using Macrobrachium rosenbergii Nodavirus-like Particles: A Systematic Review

Abstract

Virus-like particles (VLPs) are nanoscale platforms that can be engineered for heterologous molecule display. Among the available VLP platforms, Macrobrachium rosenbergii nodavirus-derived VLPs (MrNV VLPs) have emerged as a promising system for this purpose. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, 20 eligible studies were identified and qualitatively synthesized to summarize the current design strategies used for heterologous molecule display on MrNV VLPs, with a particular focus on how insert characteristics influence the selection of design strategies. The protruding (P) domain, located at the C-terminal region, serves as the main site for heterologous display. Different strategies, including genetic fusion, peptide insertion, and domain replacement, are applied depending on the size and structural complexity of the insert. Across the available studies, these approaches enabled the display of both small peptides and larger protein domains, with particle architecture maintained in studies that directly evaluated and reported VLP formation. In addition to design strategies, physicochemical properties, including structural stability, are important considerations that may influence platform performance. However, several studies did not directly report VLP assembly, and the available evidence remains heterogeneous and predominantly preclinical. Together, this review highlights the relationship between insert characteristics and design strategies in MrNV VLPs and provides insights for the rational design of VLP-based heterologous molecule display platforms for biomedical applications.