Development of “CLAN” Nanomedicine for Nucleic Acid Therapeutics

Nucleic acid‐based macromolecules have paved new avenues for the development of therapeutic interventions against a spectrum of diseases; however, their clinical translation is limited by successful delivery to the target site and cells. Therefore, numerous systems have been developed to overcome delivery challenges to nucleic acids. From the viewpoint of clinical translation, it is highly desirable to develop systems with clinically validated materials and controllability in synthesis. With this in mind, a cationic lipid assisted PEG‐b‐PLA nanoparticle (CLAN) is designed that is capable of protecting nucleic acids via encapsulation inside the aqueous core, and delivers them to target cells, while maintaining or improving nucleic acid function. The system is formulated from clinically validated components (PEG‐b‐PLA and its derivatives) and can be scaled‐up for large scale manufacturing, offering potential for its future use in clinical applications. Here, the development and working mechanisms of CLANs, the ways to improve its delivery efficacy, and its application in various disease treatments are summarized. Finally, a prospective for the further development of CLAN is also discussed. A cationic lipid assisted PEG‐b‐PLA nanoparticle (CLAN) has been developed via encapsulation of nucleic acids inside the aqueous core for disease treatment. In this Review, the development and working mechanisms of CLANs, the ways to improve its delivery efficacy, and their application are summarized. Finally, the prospective for further development of CLAN is also discussed.