What type of study is this?

September 10, 2025

Construction of ROS-Responsive Poly(β-amino ester)-poly(β-thioether ester) Copolymer for Enhancing Gene Delivery and Gene Therapy

QLQianru LiJiangnan University YZYuhe ZhuHuazhong University of Science and Technology JDJiahui DingXuzhou Medical College

Key Points

PBAE-TE2–5 copolymer achieved transfection efficiency of 75% in SiHa and 79% in HeLa cells, indicating enhanced performance.
The optimized copolymer outperformed standard poly(β-amino ester) across multiple cell lines, showing its broad applicability in gene delivery.
The introduction of thioether bonds mitigates the impact of reactive oxygen species, further improving transfection efficiency and penetration.
PBAE-TE2–5-CRISPR/Cas9 complexes effectively edited target genes and inhibited cancer cell growth, underlining its therapeutic potential.

Abstract

Gene therapy is often limited by gene vectors. To reduce the impact of intracellular reactive oxygen species and improve transfection efficiency, thioether bonds were introduced in poly(β-amino ester) (PBAE), a well-known nonviral gene vector, to synthesize PBAE-poly(β-thioether ester) copolymer (PBAE-TE). By varying the monomer feeding ratio and reaction time, the optimized copolymer (PBAE-TE2–5) showed the highest transfection efficiency in SiHa and HeLa cells (75.00 and 78.70%) with a 75:1 copolymer/GFP ratio. PBAE-TE2–5 also demonstrated superior transfection performance compared to PBAE in multiple cell lines (HeLa, Me180, C666–1, and HEK 293T) and better penetration capability in 3D spheroid cell models (SiHa and HEK 293T). The PBAE-TE2–5-CRISPR/Cas9 plasmid polyplexes could effectively edit target genes in HEK 293T (MUC2) and SiHa (HPV16 E7) cells, and inhibit cancer cell proliferation both in vitro and in vivo. These findings highlight the promising potential of PBAE-TE as an effective gene delivery system.

Ask AI

Helpful

Bookmark

View Full Paper