ROTAC technology has advantages such as targeting non-druggable targets, high catalytic activity, and overcoming drug resistance, making it a new strategy in drug development. Traditional PROTAC design and synthesis require a significant amount of time and resources, limiting its application in drug development. To address these limitations, researchers have actively explored the development of more specific and potent PROTAC molecules. In this situation, the research group led by Li Zigang and Yin Feng proposed a novel Split-and-Mix nanoscale self-regulating platform (SM-PROTAC), which offers advantages such as easy screening of input assembly molecules, adjustable assembly molecule ratios, high universality, and time savings. However, the effective degradation concentration of peptide-based SM-PROTAC is relatively high.
To find a more suitable system for the SM concept, the research group developed a new lipid-based Split-and-Mix nanoscale self-regulating platform (LipoSM-PROTAC). Validation in the biological field revealed that its effective concentration is 50–100 times lower than that of peptide-based SM-PROTAC. It also possesses characteristics of folate-selective delivery, enabling precise targeting of specific cell lines, demonstrating excellent biosafety, and holding significant clinical translation potential. It is widely applicable in various biological application areas. The research results, titled “Selective Protein of Interest (POI) degradation through split-and-mix liposome PROTAC approach”, were published in the Journal of the American Chemical Society and were selected as the cover article.
In this study, the researchers introduce a unique method that involves split-and-mix liposomes for PROTAC delivery. Liposomes, which are lipid-based vesicles, are used as carriers for delivering PROTAC molecules to the target cells. The split-and-mix strategy enhances the selectivity of protein degradation by allowing the assembly of liposomes with specific recognition elements tailored for the POI.
The research aims to achieve selective and efficient protein degradation, a critical aspect in therapeutic interventions for various diseases, including cancer. The utilization of liposomes as carriers offers advantages in terms of drug delivery, and the split-and-mix strategy provides a customizable and precise approach to tailor PROTAC delivery for specific protein targets.
The research group is currently conducting in vivo studies based on the LipoSM-PROTAC platform. Simultaneously, they are actively searching for more effective SM carriers, such as polylactic acid (PLA) and dendrimers, in the hope of developing carrier molecules that are more potent and clinically translatable. The research group’s investigations are not limited to protein degradation through the proteasome. They are continuously developing various biodegrading agents, such as Lytac, Ribotac, and Autotac, to achieve effective degradation of a variety of target molecules.
In summary, the Li Zigang and Yin Feng research group will continue to explore applications in various fields based on the SM system, bringing more innovation and breakthroughs to the field of biomedicine.