Self‐Assembling Cationic Lipopeptides for the Construction of Functional Vesicular Gene‐Delivery Systems

ABSTRACT Delivering nucleic acids across cellular membranes remains a central challenge. Although synthetic gene carriers that mimic living cells are gaining interest, creating robust and biocompatible compartments continues to be technically demanding and limited in scope. Here, we present a new class of cationic lipopeptides that self‐assemble into stable, functional membrane structures, offering a versatile platform for gene‐delivery applications. These lipopeptides combine the biological activity and programmability of peptides with the self‐organizing behavior of lipids, yielding functional vesicular structures that emulate cellular compartments and act as powerful non‐viral vectors. We demonstrate that these assemblies efficiently sequester and deliver nucleic acids, achieving high transfection efficiency with minimal cytotoxicity in HEK 293T cells, and importantly, extending this performance to more challenging cellular models such as mesenchymal stem cells (MSCs). Our findings highlight the potential of self‐assembling cationic lipopeptides as modular building blocks for generating robust, biocompatible, and programmable synthetic cells capable of delivering diverse nucleic acids.