Biophysical considerations for designing viruses, lipid nanoparticles and virus-like particles for CRISPR-based genome editing.
CRISPR-based genome editing has opened new pathways towards precision medicine, but its success depends on more than just molecular engineering. Cargo and carrier dynamics are profoundly influenced by the underlying biophysical properties of cells and vectors. Consequently, this domain is moving beyond simple "lock and key" approaches, and towards disease-customised fits. In this review, we examine how biophysical properties of viral vectors, lipid nanoparticles, and hybrid virus-like particles influence editor delivery performance. We examine parameters such as size, cargo capacity, charge, shape, stiffness, membrane composition, internalisation strategies, tropism, endosomal escape, protein corona formation, and immune recognition as key drivers of intelligent, modular engineering. Finally, we explore how the notion of carrier systems shifts in diseased states like solid tumour cancers, autoimmune psoriasis of the skin, and the autosomal monogenic cystic fibrosis, where altered biophysical landscapes demand adaptable, context-informed genome editing solutions.