Pyridinium cationic lipids in gene delivery: an in vitro and in vivo comparison of transfection efficiency versus a tetraalkylammonium congener

2005 ◽  
Vol 435 (1) ◽  
pp. 217-226 ◽  
Author(s):  
Marc A. Ilies ◽  
Betty H. Johnson ◽  
Fred Makori ◽  
Aaron Miller ◽  
William A. Seitz ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Transfection Efficiency ◽  
Cationic Lipids

Evaluation of low molecular weight polyethylenimine-introduced chitosan for gene delivery to mesenchymal stem cells

2020 ◽  
Vol 10 (7) ◽  
pp. 1170-1176
Author(s):  
Minchen Liu ◽  
Yulan Hu ◽  
Yi Feng
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Gene Delivery ◽  
Transfection Efficiency ◽  
A549 Cells ◽  
Safety Evaluation ◽  
Physicochemical Characteristics ◽  
Hatching Rate

This study aimed to examine the transfection ability of polyethylenimine (PEI) (1800 Da)-grafted chitosan (10 kDa) (CP), a newly synthesized PEI derivative, in mesenchymal stem cells (MSCs). The safety evaluation of the complex/DNA was studied in vitro and in vivo. In addition, CP/pGL3 was applied to investigate the effects of transfection efficiency. In this study, CP/DNA can be formed with compatible physicochemical characteristics for gene delivery. CP cytotoxicity decreased in A549 cells. Moreover, a zebrafish embryo model was used for evaluating the safety in vivo. Compared to the PEI (25 kDa) group, the zebrafish hatching rate increased and the mortality rate decreased in the CP/DNA group, which provided an indication of the safety of CP. In comparison with chitosan (100 kDa)-PEI (1200 Da), CP's transfection efficiency was higher in both A549 cells and MSCs. This study aimed to lay the foundation for further applications of CP in gene delivery. Therefore, further gene therapy investigations of CP by using MSCs need to be performed.

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 ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Delivery System ◽  
Transfection Efficiency ◽  
Viral Gene ◽  
Gene Delivery System ◽  
Targeted Gene Delivery ◽  
Cell Specificity ◽  
Selective Delivery

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.

scholarly journals Exploitation of De Novo Helper-Lipids for Effective Gene Delivery.

2009 ◽  
Vol 11 (4) ◽  
pp. 56 ◽  
Author(s):  
Tomoaki Kurosaki ◽  
Takashi Kitahara ◽  
Mugen Teshima ◽  
Koyo Nishida ◽  
Junzo Nakamura ◽  
...  
Keyword(s):  
Gene Delivery ◽  
De Novo ◽  
Transfection Efficiency ◽  
The Other ◽  
Penetration Enhancers ◽  
Cell Toxicity ◽  
In Vivo Transfection ◽  
In Vitro Transfection

Purpose: In gene delivery, a fusogenic lipid such as dioleyl phosphatidylethanolamine (DOPE) which is a component of cationic liposomal vector is important factor for effective transfection efficiency. We investigated the effect of penetration enhancers as alternative helper-lipids to DOPE. Methods: Transdermal penetraion enhancers such as N-lauroylsarcosine (LS), (R)-(+)-limonene (LM), vitamin E (VE), and phosphatidyl choline from eggs (EggPC) were used in this experiments as helper-lipids with N-[1-(2, 3-dioleyloxy) propyl]-N, N, N-trimethlylammonium chloride (DOTMA) and cholesterol (CHOL). We examined in vitro transfection efficiency, cytotoxicity, hematotoxicity, and in vivo transfection efficiency of plasmid DNA/cationic liposomes complexes. Results: In transfection experiments in vitro, the cationic lipoplexes containing LS had highest transfection efficiency among the other lipoplexes independently of FBS. Furthermore, the lipoplexes containing LS had lowest cell toxicity among the other lipoplexes in the presence of FBS. As the results of erythrocytes interaction experiment, DOTMA/LS/CHOL, DOTMA/VE/CHOL, and DOTMA/EggPC/CHOL lipoplexes showed extremely lower hematotoxicity. On the basis of these results, the in vivo transfection efficiencies of the lipoplexes were examined. The lipoplexes containing LS had the highest transfection activity among the other lipoplexes. Conclusion: In conclusion, several transdermal penetration enhancers are available for alternative helper-lipids to DOPE in cationic liposomal vectors. Among them, DOTMA/LS/CHOL lipoplexes showed superior characteristics in in vitro transfection efficiency, cell toxicity, hematotoxicity, and in vivo transfection efficiency.

scholarly journals Interaction kinetics of peptide lipids-mediated gene delivery

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Yinan Zhao ◽  
Tianyi Zhao ◽  
Yanyan Du ◽  
Yingnan Cao ◽  
Yang Xuan ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Endosomal Escape ◽  
Late Endosomes ◽  
Key Factor ◽  
Interaction Kinetics ◽  
Dna Release

Abstract Background During the course of gene transfection, the interaction kinetics between liposomes and DNA is speculated to play very important role for blood stability, cellular uptake, DNA release and finally transfection efficiency. Results As cationic peptide liposomes exhibited great gene transfer activities both in vitro and in vivo, two peptide lipids, containing a tri-ornithine head (LOrn3) and a mono-ornithine head (LOrn1), were chosen to further clarify the process of liposome-mediated gene delivery in this study. The results show that the electrostatically-driven binding between DNA and liposomes reached nearly 100% at equilibrium, and high affinity of LOrn3 to DNA led to fast binding rate between them. The binding process between LOrn3 and DNA conformed to the kinetics equation: y = 1.663631 × exp (− 0.003427x) + 6.278163. Compared to liposome LOrn1, the liposome LOrn3/DNA lipoplex exhibited a faster and more uniform uptake in HeLa cells, as LOrn3 with a tri-ornithine peptide headgroup had a stronger interaction with the negatively charged cell membrane than LOrn1. The efficient endosomal escape of DNA from LOrn3 lipoplex was facilitated by the acidity in late endosomes, resulting in broken carbamate bonds, as well as the “proton sponge effect” of the lipid. Conclusions The interaction kinetics is a key factor for DNA transfection efficiency. This work provided insights into peptide lipid-mediated DNA delivery that could guide the development of the next generation of delivery systems for gene therapeutics.

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

2007 ◽  
Vol 539-543 ◽  
pp. 641-646 ◽  
Author(s):  
Tae Hee Kim ◽  
Jin Hua ◽  
Hyun Woo Kim ◽  
Myung Haing Cho ◽  
Jae Woon Nah ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Delivery System ◽  
Transfection Efficiency ◽  
Viral Gene ◽  
Gene Delivery System ◽  
Targeted Gene Delivery ◽  
Cell Specificity ◽  
Selective Delivery

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.

Functional Amphiphiles for Gene Delivery

MRS Bulletin ◽  
2005 ◽  
Vol 30 (9) ◽  
pp. 647-653 ◽  
Author(s):  
Philippe Barthélémy ◽  
Michel Camplo
Keyword(s):  
Gene Transfer ◽  
Gene Delivery ◽  
Viral Vectors ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Research Activity ◽  
Safety Issues ◽  
Significant Research

AbstractThe design of safe and efficient gene transfer vectors remains one of the key challenges in gene therapy. Despite their remarkable transfection efficiency, viral vectors suffer from known safety issues. Consequently, significant research activity has been undertaken to develop nonviral approaches to gene transfer during the last decade. Numerous academic and industrial research groups are investigating synthetic cationic vectors, such as cationic amphiphiles, with the objective of increasing the gene transfection activity. Within this area, the development of functional synthetic vectors that respond to local environmental effects have met with success. These synthetic vectors are based on mechanistic principles and represent a significant departure from earlier systems. Many of these systems for gene delivery in vitro and in vivo are discussed in this article.

scholarly journals Interaction Kinetics of Peptide Lipids-Mediated Gene Delivery

2019 ◽  
Author(s):  
Shubiao Zhang ◽  
Yinan Zhao ◽  
Yanyan Du ◽  
Yingnan Cao ◽  
Yang Xuan ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Endosomal Escape ◽  
Late Endosomes ◽  
Key Factor ◽  
Interaction Kinetics ◽  
Dna Release

Abstract Background: During the course of gene transfection, the interaction kinetics between liposomes and DNA is speculated to play very important role for blood stability, cellular uptake, DNA release and finally transfection efficiency.Results: As cationic peptide liposomes exhibited great gene transfer activities both in vitro and in vivo, two peptide lipids, containing a tri-ornithine head (LOrn3) and a mono-ornithine head (LOrn1), were chosen to further clarify the process of liposome-mediated gene delivery in this study. The results show that the electrostatically-driven binding between DNA and liposomes reached nearly 100% at equilibrium, and high affinity of LOrn3 to DNA led to fast binding rate between them. The binding process between LOrn3 and DNA conformed to the kinetics equation: y = 1.663631 × exp(-0.003427x) + 6.278163. Compared to liposome LOrn1, the liposome LOrn3/DNA lipoplex exhibited a faster and more uniform uptake in Hela cells, as LOrn3 with a tri-ornithine peptide headgroup had a stronger interaction with the negatively charged cell membrane than LOrn1. The efficient endosomal escape of DNA from LOrn3 lipoplexes was facilitated by the acidity in late endosomes, resulting in broken carbamate bonds, as well as the “proton sponge effect” of the lipid.Conclusions: The interaction kinetics is a key factor for DNA transfection efficiency. This work provided insights into peptide lipid-mediated DNA delivery that could guide the development of the next generation of delivery systems for gene therapeutics.

The Combination of Drug or Gene Delivery System Responding to Cellular Signals (D-RECS) and Sonoporation System for Effective and Safe Gene Delivery

2009 ◽  
Vol 1237 ◽  
Author(s):  
Akira Tsuchiya ◽  
Takeshi Mori ◽  
Yuki Naritomi ◽  
Jeong-Hun Kang ◽  
Daisuke Asai ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Gene Delivery ◽  
Delivery System ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Regulation System ◽  
Gene Delivery System

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.

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