Characterization of a multifunctional PEG-based gene delivery system containing nuclear localization signals and endosomal escape peptides

2009 ◽  
Vol 5 (3) ◽  
pp. 854-864 ◽  
Author(s):  
Nicole M. Moore ◽  
Clayton L. Sheppard ◽  
Shelly E. Sakiyama-Elbert
2017 ◽  
Vol 2017 ◽  
pp. 1-10
Author(s):  
Jingjing Cui ◽  
Qing Deng ◽  
Qing Zhou ◽  
Sheng Cao ◽  
Nan Jiang ◽  
...  

Objective. This study aimed to develop a gene delivery system using ultrasound-targeted microbubbles destruction (UTMD) combined with nuclear localization signal (NLS) and investigate its efficacy and safety for therapeutic angiogenesis in canine myocardial infarction (MI) model. Methods. Fifty MI dogs were randomly divided into 5 groups and transfected with Ang-1 gene plasmid: (i) group A: only injection of microbubbles and Ang-1 plasmid; (ii) group B: only UTMD mediated gene transfection; (iii) group C: UTMD combined with classical NLS mediated gene transfection; (iv) group D: UTMD combined with mutational NLS mediated transfection; and (v) group E: UTMD combined with classical NLS in the presence of a nucleus transport blocker. The mRNA and protein expression of Ang-1 gene, microvessel density (MVD) cardiac troponin I (cTnI), and cardiac function were determined after transfection. Results. The expression of mRNA and protein of Ang-1 gene in group C was significantly higher than that of the other groups (all P < 0.01). The MVD of group C was 10.2-fold of group A and 8.1-fold of group E (P < 0.01). The cardiac function in group C was significant improvement without cTnI rising. Conclusions. The gene delivery system composed of UTMD and NLS is efficient and safe.


2020 ◽  
Vol 8 (33) ◽  
pp. 7475-7482
Author(s):  
De-E Liu ◽  
Xiangjie Yan ◽  
Jinxia An ◽  
Jianbiao Ma ◽  
Hui Gao

A novel virus-mimicking gene delivery system with excellent endosomal escape, efficient transfection, and traceability is developed which can serve as a reference for the construction of novel multifunctional efficient gene delivery systems.


Pharmaceutics ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 608 ◽  
Author(s):  
Guan ◽  
Song ◽  
Zhang ◽  
Chen ◽  
Hu ◽  
...  

Considerable effort has been devoted to the development of gene carriers over the years. However, toxicity, immunogenicity, and low transfection efficiency are still major barriers. How to overcome these obstacles has become a burning question in gene delivery. In the present study, a simple cationic human serum albumin (CHSA)-based gene-delivery system containing nuclear localization signals (NLSs) was constructed to conquer the limitations. CHSA/NLS/plasmid DNA (pDNA) complexes were prepared and characterized by Hoechst 33258 intercalation, gel retardation assay, morphological analysis, circular dichroism (CD) spectroscopy, particle size, and zeta potential measurements. Results showed that CHSA/NLS/pDNA complexes were able to condense and protect pDNA with high encapsulation efficiency. The complexes displayed a nutritional effect on cells at a low concentration and there was no significant cytotoxicity or immunogenicity. In addition, CHSA/NLS/pDNA complexes exhibited excellent cellular uptake rates and the mechanism was mainly the clathrin or macropinocytosis-dependent endocytosis pathway. Furthermore, CHSA/NLS/pDNA significantly enhanced gene expression efficiency in vitro. More importantly, CHSA/NLS/pDNA complexes showed a desired antitumor effect in vivo, exhibiting the highest inhibition rate (57.3%) and significant upregulation in p53 protein. All these results confirm that CHSA/NLS/pDNA complexes have a bright future as a safe and effective delivery system for gene therapy.


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