Interaction kinetics of peptide lipids-mediated gene delivery

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.

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Interaction Kinetics of Peptide Lipids-Mediated Gene Delivery

10.21203/rs.2.18224/v1 ◽

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.

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Interaction Kinetics of Peptide Lipids-Mediated Gene Delivery

10.21203/rs.2.18224/v4 ◽

2020 ◽

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.

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Interaction Kinetics of Peptide Lipids-Mediated Gene Delivery

10.21203/rs.2.18224/v3 ◽

2020 ◽

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.

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Interaction Kinetics of Peptide Lipids-Mediated Gene Delivery

10.21203/rs.2.18224/v2 ◽

2020 ◽

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.

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Combining Hyaluronic Acid with Chitosan Enhances Gene Delivery

Journal of Nanomaterials ◽

10.1155/2014/246347 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 10

Author(s):

Ana V. Oliveira ◽

Diogo B. Bitoque ◽

Gabriela A. Silva

Keyword(s):

Hyaluronic Acid ◽

Gene Delivery ◽

Transfection Efficiency ◽

Gene Transfection ◽

Retinal Pigment ◽

Retinal Pigment Epithelial Cells ◽

Nonviral Vectors ◽

Anionic Polymer ◽

Dna Release

The low gene transfer efficiency of chitosan-DNA polyplexes is a consequence of their high stability and consequent slow DNA release. The incorporation of an anionic polymer is believed to loosen chitosan interactions with DNA and thus promote higher transfection efficiencies. In this work, several formulations of chitosan-DNA polyplexes incorporating hyaluronic acid were prepared and characterized for their gene transfection efficiency on both HEK293 and retinal pigment epithelial cells. The different polyplex formulations showed morphology, size, and charge compatible with a role in gene delivery. The incorporation of hyaluronic acid rendered the formulations less stable, as was the goal, but it did not affect the loading and protection of the DNA. Compared with chitosan alone, the transfection efficiency had a 4-fold improvement, which was attributed to the presence of hyaluronic acid. Overall, our hybrid chitosan-hyaluronic acid polyplexes showed a significant improvement of the efficiency of chitosan-based nonviral vectorsin vitro, suggesting that this strategy can further improve the transfection efficiency of nonviral vectors.

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Functional Amphiphiles for Gene Delivery

MRS Bulletin ◽

10.1557/mrs2005.191 ◽

2005 ◽

Vol 30 (9) ◽

pp. 647-653 ◽

Cited By ~ 9

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.

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

MRS Proceedings ◽

10.1557/proc-1237-tt05-11 ◽

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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Non-Viral Vectors for Gene Delivery

Nanoscience &Nanotechnology-Asia ◽

10.2174/2210681208666180110154233 ◽

2018 ◽

Vol 9 (1) ◽

pp. 4-11 ◽

Cited By ~ 5

Author(s):

Aparna Bansal ◽

Himanshu

Keyword(s):

Gene Therapy ◽

Viral Vectors ◽

Transfection Efficiency ◽

Gene Transfection ◽

Expression System ◽

Target Cells ◽

Specific Expression ◽

Naked Dna

Introduction: Gene therapy has emerged out as a promising therapeutic pave for the treatment of genetic and acquired diseases. Gene transfection into target cells using naked DNA is a simple and safe approach which has been further improved by combining vectors or gene carriers. Both viral and non-viral approaches have achieved a milestone to establish this technique, but non-viral approaches have attained a significant attention because of their favourable properties like less immunotoxicity and biosafety, easy to produce with versatile surface modifications, etc. Literature is rich in evidences which revealed that undoubtedly, non–viral vectors have acquired a unique place in gene therapy but still there are number of challenges which are to be overcome to increase their effectiveness and prove them ideal gene vectors. Conclusion: To date, tissue specific expression, long lasting gene expression system, enhanced gene transfection efficiency has been achieved with improvement in delivery methods using non-viral vectors. This review mainly summarizes the various physical and chemical methods for gene transfer in vitro and in vivo.

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Retracted Article: A multifunctional self-dissociative polyethyleneimine derivative coating polymer for enhancing the gene transfection efficiency of DNA/polyethyleneimine polyplexes in vitro and in vivo

Polymer Chemistry ◽

10.1039/c4py01135j ◽

2015 ◽

Vol 6 (5) ◽

pp. 780-796 ◽

Cited By ~ 36

Author(s):

Cheng Wang ◽

Xiuli Bao ◽

Xuefang Ding ◽

Yang Ding ◽

Sarra Abbad ◽

...

Keyword(s):

Transfection Efficiency ◽

Gene Transfection ◽

Retracted Article ◽

First Time

A novel coating polymer LPHF is developed for the first time to elevate the transfection efficiency of DP binary polyplexes in vitro and in vivo.

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Aliphatic Quaternary Ammonium Functionalized Nanogels for Gene Delivery

Pharmaceutics ◽

10.3390/pharmaceutics13111964 ◽

2021 ◽

Vol 13 (11) ◽

pp. 1964

Author(s):

Huaiying Zhang ◽

Damla Keskin ◽

Willy H. de Haan-Visser ◽

Guangyue Zu ◽

Patrick van Rijn ◽

...

Keyword(s):

Gene Delivery ◽

Tertiary Amine ◽

Quaternary Ammonium ◽

Gene Transfection ◽

Genetic Material ◽

Cationic Lipid ◽

Endosomal Escape ◽

Hereditary Diseases ◽

Viral Gene

Gene therapy is a promising treatment for hereditary diseases, as well as acquired genetic diseases, including cancer. Facing the complicated physiological and pathological environment in vivo, developing efficient non-viral gene vectors is needed for their clinical application. Here, poly(N-isopropylacrylamide) (p(NIPAM)) nanogels are presented with either protonatable tertiary amine groups or permanently charged quaternized ammonium groups to achieve DNA complexation ability. In addition, a quaternary ammonium-functionalized nanogel was further provided with an aliphatic moiety using 1-bromododecane to add a membrane-interacting structure to ultimately facilitate intracellular release of the genetic material. The ability of the tertiary amine-, quaternized ammonium-, and aliphatic quaternized ammonium-functionalized p(NIPAM) nanogels (i.e., NGs, NGs-MI, and NGs-BDD, respectively) to mediate gene transfection was evaluated by fluorescence microscopy and flow cytometry. It is observed that NGs-BDD/pDNA complexes exhibit efficient gene loading, gene protection ability, and intracellular uptake similar to that of NGs-MI/pDNA complexes. However, only the NGs-BDD/pDNA complexes show a notable gene transfer efficiency, which can be ascribed to their ability to mediate DNA escape from endosomes. We conclude that NGs-BDD displays a cationic lipid-like behavior that facilitates endosomal escape by perturbing the endosomal/lysosomal membrane. These findings demonstrate that the presence of aliphatic chains within the nanogel is instrumental in accomplishing gene delivery, which provides a rationale for the further development of nanogel-based gene delivery systems.

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