Citation: Zhili Li, Qijun Wo, Dongdong Huang, Dezhong Zhou, Lei Guo, Yeqing Mao. Improving gene transfection efficiency of highly branched poly(β-amino ester)s through the in-situ conversion of inactive terminal groups[J]. Chinese Chemical Letters, ;2024, 35(8): 109737. doi: 10.1016/j.cclet.2024.109737 shu

Improving gene transfection efficiency of highly branched poly(β-amino ester)s through the in-situ conversion of inactive terminal groups

Zhili Li ^{a, b} ,
Qijun Wo ^{c, d} ,
Dongdong Huang ^e ,
Dezhong Zhou ^{b, *,} ,
Lei Guo ^{e, *,} ,
Yeqing Mao ^{a, *,}

a.
Department of Urology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310000, China
b.
School of Chemical Engineering and Technology, Xi'an Jiaotong University, Xi'an 710049, China
c.
Urology & Nephrology Center, Department of Urology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou 310014, China
d.
Key Laboratory of Endocrine Gland Diseases of Zhejiang Province, Hangzhou 310014, China
e.
Pooling Institute of Translational Medicine, Hangzhou 311100, China

dezhong.zhou@xjtu.edu.cn

lincguo@100biotech.com

598725073@qq.com

Received Date: 30 November 2023
Revised Date: 16 February 2024
Accepted Date: 21 February 2024
Available Online: 6 March 2024

Figures(4)

Highly branched poly(β-amino ester)s (HPAEs) have emerged as a safe and efficient type of non-viral gene delivery vectors. However, the presence of inactive terminal secondary amine groups compromises their gene transfection capability. In this study, HPAEs with similar topological structures and chemical compositions but varying numbers of terminal secondary 4-amino-1-butanol (S4) and secondary/tertiary 3-morpholinopropylamine (MPA) groups were synthesized. The results demonstrate that an increased number of secondary/tertiary MPA groups in-situ significantly enhances the DNA binding capability of HPAEs, leading to the formation of smaller HPAE/DNA polyplexes with higher zeta potential, ultimately resulting in superior gene transfection efficiency in bladder epithelial cells. This study establishes a simple yet effective strategy to maximize the gene transfection potency of HPAEs by converting the inactive terminal groups in-situ without the need for complex modifications to their topological structure and chemical composition.
- Gene therapy,
- Gene delivery vector,
- Highly branched poly(β-amino ester)s,
- Terminal groups,
- Epithelial cells
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