Multifunctional degradable highly branched-linear poly(β-amino esters) for efficient YAP gene delivery

Area of Science:

• Polymer Chemistry
• Gene Therapy
• Oncology

Background:

• The Yes-associated protein (YAP) gene is crucial for cancer pathogenesis and skin tissue repair.
• Developing safe and efficient YAP gene delivery systems is essential for clinical applications but remains challenging.

Purpose of the Study:

• To synthesize novel highly branched-linear poly(β-amino esters) (H-LPAEs) for efficient YAP gene delivery.
• To evaluate the transfection efficiency and safety profile of synthesized H-LPAEs in cancer cells.

Main Methods:

• A two-step linear oligomer combination branching strategy was used to synthesize H-LPAEs.
• Gene transfection efficiency was assessed using RT-PCR and western blot analyses.
• Cytotoxicity assays were performed to evaluate the safety profile.

Main Results:

• H-LPAE-1 demonstrated exceptional gene transfection efficiency, reaching up to 76.6% across various cell types.
• The synthesized H-LPAEs effectively condensed DNA into nanosized polyplexes, facilitating cellular uptake.
• H-LPAE-1 showed a superior safety profile and highly efficient YAP DNA delivery in cutaneous squamous cell carcinoma (SCC).

Conclusions:

• The study presents a novel and easy-to-operate "oligomer combination branching strategy" for synthesizing H-LPAEs.
• H-LPAE-1 is identified as a promising candidate for effective YAP gene delivery in cancer therapy and tissue regeneration.