Receptor-Mediated Gene Delivery Using Chitosan Derivatives In Vitro and In Vivo

2007 ◽  
Vol 342-343 ◽  
pp. 449-452 ◽  
Author(s):  
Tae Hee Kim ◽  
Hua Jin ◽  
Hyun Woo Kim ◽  
Myung Haing Cho ◽  
Jae Woon Nah ◽  
...  

The key strategy for the advancement of gene therapy is the development of an efficient targeted gene delivery system into cells. The targeted gene delivery system is especially important in non-viral gene transfer which shows the relatively low transfection efficiency. It also opens the possibility of selective delivery of therapeutic plasmids to specific tissues. Chitosan has been considered to be a good candidate for gene delivery system, since it is already known as a biocompatible, biodegradable, and low toxic material with high cationic potential. However, low specificity and low transfection efficiency of chitosan need to be overcome prior to clinical trial. In this study, we focused on the chemical modification of chitosan for enhancement of cell specificity and transfection efficiency. Also, the potential of clinical application was investigated.


2007 ◽  
Vol 539-543 ◽  
pp. 641-646 ◽  
Author(s):  
Tae Hee Kim ◽  
Jin Hua ◽  
Hyun Woo Kim ◽  
Myung Haing Cho ◽  
Jae Woon Nah ◽  
...  

The development of an efficient targeted gene delivery system into cells is an important strategy for the advancement of gene therapy. The targeted gene delivery system is especially important in non-viral gene transfer which shows the relative low transfection efficiency. And it also opens the possibility of selective delivery of therapeutic plasmids to specific tissues. Chitosan has been considered to be a good candidate for gene delivery system, since it is already known as a biocompatible, biodegradable, and low toxic material with high cationic potential. However, low specificity and low transfection efficiency of chitosan need to be overcome prior to clinical trial. In this study, we focused on the chemical modification of chitosan for enhancement of cell specificity and transfection efficiency.



2006 ◽  
Vol 17 (1) ◽  
pp. 152-158 ◽  
Author(s):  
Kokhou Wong ◽  
Guobin Sun ◽  
Zhang ◽  
Hui Dai ◽  
Ye Liu ◽  
...  


2009 ◽  
Vol 1237 ◽  
Author(s):  
Akira Tsuchiya ◽  
Takeshi Mori ◽  
Yuki Naritomi ◽  
Jeong-Hun Kang ◽  
Daisuke Asai ◽  
...  

AbstractWe have developed new gene expression-regulating polymer that can activate transgene expression in response to target intracellular signals. Here, we tried applying sonoporation system to this gene regulation system to enhance the gene expression efficacy. Sonoporation is the method for effective gene transfection in vitro and in vivo. Therefore, the method might enhance the transfection efficiency in our polymer and realize an efficient and safe gene delivery system. Results suggested that the combination of our polymer and sonoporation could improve the gene expression compared to the system using only our polymer that transfers genes into cells via endocytosis. It also kept the ability of the gene regulation responding to cellular signals.



2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Guicun Wu ◽  
Fang Zhou ◽  
Linfu Ge ◽  
Ximin Liu ◽  
Fansheng Kong

Purpose. Biodegradable polymeric nanoparticles have been used frequently as gene delivery vehicles. The aim of this study is to modify bioadhesive PLGA nanoparticles with novel synthetic mannan-PEG-PE (MN-PEG-PE) to obtain active targeted gene delivery system.Methods. Mannan-PEG-PE ligands were synthesized and modified onto the NPs/pEGFP complexes. The modification rate was optimized, and the characteristics of the vehicle were evaluated. Then, the modified vectors were intravenous delivered to rats, andin vivotargeting behavior of MN-PEG-PE modified PLGA nanoparticles/pEGFP complexes (MN-PEG-PE-NPs/pEGFP) in liver macrophages was investigated.Results. MN-PEG-PE-NPs/pEGFP displayed remarkably higher transfection efficiencies than nonmodified NPs/pEGFP bothin vitroandin vivo.Conclusions. Mannan containing targeting ligands could significantly improve the transfection efficiency of the carriers. MN-PEG-PE modified vectors very useful in targeted gene delivery.







2006 ◽  
Vol 13 ◽  
pp. S291
Author(s):  
Dima Sheyn ◽  
Gadi Pelled ◽  
Yoram Zilberman ◽  
Zulma Gazit ◽  
Dan Gazit


2021 ◽  
Vol 22 (8) ◽  
pp. 3828
Author(s):  
Laura Nicolle ◽  
Jens Casper ◽  
Melanie Willimann ◽  
Céline M. A. Journot ◽  
Pascal Detampel ◽  
...  

There is an increasing interest in cationic polymers as important constituents of non-viral gene delivery vectors. In the present study, we developed a versatile synthetic route for the production of covalent polymeric conjugates consisting of water-soluble depolymerized chitosan (dCS; MW 6–9 kDa) and low molecular weight polyethylenimine (PEI; 2.5 kDa linear, 1.8 kDa branched). dCS-PEI derivatives were evaluated based on their physicochemical properties, including purity, covalent bonding, solubility in aqueous media, ability for DNA condensation, and colloidal stability of the resulting polyplexes. They were complexed with non-integrating DNA vectors coding for reporter genes by simple admixing and assessed in vitro using liver-derived HuH-7 cells for their transfection efficiency and cytotoxicity. Using a rational screening cascade, a lead compound was selected (dCS-Suc-LPEI-14) displaying the best balance of biocompatibility, cytotoxicity, and transfection efficiency. Scale-up and in vivo evaluation in wild-type mice allowed for a direct comparison with a commercially available non-viral delivery vector (in vivo-jetPEI). Hepatic expression of the reporter gene luciferase resulted in liver-specific bioluminescence, upon intrabiliary infusion of the chitosan-based polyplexes, which exceeded the signal of the in vivo jetPEI reference formulation by a factor of 10. We conclude that the novel chitosan-derivative dCS-Suc-LPEI-14 shows promise and potential as an efficient polymeric conjugate for non-viral in vivo gene therapy.



2013 ◽  
Vol 50 (3-4) ◽  
pp. 484-491 ◽  
Author(s):  
Diego Delgado ◽  
Ana del Pozo-Rodríguez ◽  
M. Angeles Solinís ◽  
Artur Bartkowiak ◽  
Alicia Rodríguez-Gascón


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