Scheme of different strategies for cargo loading into the P22 VLP. The scheme shows common methods of cargo loading into the P22 VLP, either in vitro (after particle expression and purification) or in vivo (during particle expression inside the cell). In general, the in vitro internalization of cargo using the WB morphology is performed by an initial modification of the particle’s internal surface with a ligand molecule that will then bind to the desired cargo molecule [9,12,63]. Another method of in vitro cargo loading consists of disassembling ES particles to obtain CP subunits and mixing them with a SP–cargo fusion, promoting the assembly of P22 VLP and cargo internalization [13,65,66]. The in vivo encapsulation method consists of the coexpression of CP subunits with SP–cargo fusions, resulting in P22 VLP assembly and cargo loading inside the cell [16]. The figure was created at biorender.com.