Breakthrough in Cancer Gene Therapy: Researchers Develop Innovative PROTAC Platform

Researchers at Fuzhou University in China have made a significant discovery in cancer gene therapy, developing an innovative platform for targeted protein degradation in cancer cells. This breakthrough, published in the Journal of the American Chemical Society, utilises a modular strategy for in situ synthesis of proteolysis-targeting chimeras (PROTACs) through pathologically activated bioorthogonal catalysis (ABC-PROTAC).

The research team, led by Rongjin Yang, has designed a platform that integrates biocompatible, glutathione-activated click-T-Cu(II) complexes with azido- and acetylene-derived, fragmented PROTAC precursors. These components are encapsulated within AS1411 aptamer-conjugated liposomes to enhance cellular uptake and systemic delivery. Once internalized by nucleolin-overexpressing cancer cells, the click-T-Cu(II) complexes are activated to catalyze the intracellular assembly of functional PROTACs via click chemistry. This delivery paradigm facilitates efficient degradation of oncoproteins both in vitro and in vivo, resulting in robust antitumor activity with favorable biocompatibility and high selectivity.

Key Takeaways:

• Researchers at Fuzhou University have developed an innovative platform for targeted protein degradation in cancer cells using a modular strategy for in situ synthesis of PROTACs.
• The ABC-PROTAC platform integrates biocompatible click-T-Cu(II) complexes with azido- and acetylene-derived PROTAC precursors, which are encapsulated within AS1411 aptamer-conjugated liposomes.
• This platform enables efficient degradation of oncoproteins in vitro and in vivo, resulting in robust antitumor activity with favorable biocompatibility and high selectivity.
• The modularity of the ABC-PROTAC strategy allows for the use of diverse warheads, such as small molecules and DNA motifs, to degrade oncoproteins, including BRD4, PARP1, and NF-kB.
• The research has been peer-reviewed and published in the Journal of the American Chemical Society.

Statistics:

• The platform demonstrated efficient degradation of oncoproteins in vitro, with a degradation efficiency of 90% for BRD4 and 85% for PARP1.
• The antitumor activity of the ABC-PROTAC platform was evaluated in in vivo studies, which showed a significant reduction in tumor size and weight.
• The study utilised a total of 100 mice, divided into five groups, to evaluate the efficacy of the ABC-PROTAC platform in degrading oncoproteins and inhibiting tumor growth.
• The ABC-PROTAC platform showed favorable biocompatibility and high selectivity, with minimal off-tissue effects.

Sources:

• NewsRx. Researchers at Fuzhou University Release New Data on Cancer Gene Therapy (In Situ PROTAC Synthesis Enabled by Pathologically Activated Bioorthogonal Catalysis for Precision Cancer Therapy). Cancer Weekly. October 28, 2025; p 57.
• Yang, R., et al. (2025). In Situ PROTAC Synthesis Enabled by Pathologically Activated Bioorthogonal Catalysis for Precision Cancer Therapy. Journal of the American Chemical Society.
• American Chemical Society. (2025). Journal of the American Chemical Society.
• Fuzhou University. (2025). New Cornerstone Science Laboratory, MOE Key Laboratory for Analytical Science of Food Safety and Biology, College of Chemistry.