scholarly journals Scaling the effect of hydrophobic chain length on gene transfer properties of di-alkyl, di-hydroxy ethylammonium chloride based cationic amphiphiles

RSC Advances ◽  
2017 ◽  
Vol 7 (41) ◽  
pp. 25398-25405 ◽  
Author(s):  
Ankita A. Hiwale ◽  
Chandrashekhar Voshavar ◽  
Priya Dharmalingam ◽  
Ashish Dhayani ◽  
Rajesh Mukthavaram ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Gene Transfer ◽  
Transfection Efficiency ◽  
Systematic Investigation ◽  
Cationic Lipids ◽  
Nucleic Acid Delivery ◽  
Hydrocarbon Chains ◽  
Hydrophobic Chain ◽  
Transfer Properties

Asymmetric hydrocarbon chains influence the efficiency of cationic lipids based liposomes in nucleic acid delivery. A systematic investigation of role of asymmetry in transfection efficiency.

scholarly journals Role of Lipid-Based and Polymer-Based Non-Viral Vectors in Nucleic Acid Delivery for Next-Generation Gene Therapy

Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2866 ◽  
Author(s):  
Aniket Wahane ◽  
Akaash Waghmode ◽  
Alexander Kapphahn ◽  
Karishma Dhuri ◽  
Anisha Gupta ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Nucleic Acid ◽  
Messenger Rna ◽  
Viral Vectors ◽  
Cationic Lipids ◽  
Nucleic Acid Delivery ◽  
Nucleic Acid Analogs ◽  
Organ Specific ◽  
Interfering Rna

The field of gene therapy has experienced an insurgence of attention for its widespread ability to regulate gene expression by targeting genomic DNA, messenger RNA, microRNA, and short-interfering RNA for treating malignant and non-malignant disorders. Numerous nucleic acid analogs have been developed to target coding or non-coding sequences of the human genome for gene regulation. However, broader clinical applications of nucleic acid analogs have been limited due to their poor cell or organ-specific delivery. To resolve these issues, non-viral vectors based on nanoparticles, liposomes, and polyplexes have been developed to date. This review is centered on non-viral vectors mainly comprising of cationic lipids and polymers for nucleic acid-based delivery for numerous gene therapy-based applications.

scholarly journals Synthetic Histidine-Rich Peptides Inhibit Candida Species and Other Fungi In Vitro: Role of Endocytosis and Treatment Implications

2006 ◽  
Vol 50 (8) ◽  
pp. 2797-2805 ◽  
Author(s):  
Jingsong Zhu ◽  
Paul W. Luther ◽  
Qixin Leng ◽  
A. James Mixson
Keyword(s):  
Nucleic Acid ◽  
Antifungal Activity ◽  
Antifungal Agents ◽  
Fungal Growth ◽  
Nucleic Acid Delivery ◽  
Histatin 5 ◽  
Ph Buffering ◽  
Endosomal Acidification

ABSTRACT A family of histidine-rich peptides, histatins, is secreted by the parotid gland in mammals and exhibits marked inhibitory activity against a number of Candida species. We were particularly interested in the mechanism by which histidine-rich peptides inhibit fungal growth, because our laboratory has synthesized a variety of such peptides for drug and nucleic acid delivery. In contrast to naturally occurring peptides that are linear, peptides made on synthesizers can be varied with respect to their degrees of branching. Using this technology, we explored whether histidine-lysine (HK) polymers of different complexities and degrees of branching affect the growth of several species of Candida. Polymers with higher degrees of branching were progressively more effective against Candida albicans, with the four-branched polymer, H2K4b, most effective. Furthermore, H2K4b accumulated efficiently in C. albicans, which may indicate its ability to transport other antifungal agents intracellularly. Although H2K4b had greater antifungal activity than histatin 5, their mechanisms were similar. Toxicity in C. albicans induced by histatin 5 or branched HK peptides was markedly reduced by 4,4′-diisothiocyanato-stilbene-2,2′-disulfonate, an inhibitor of anion channels. We also determined that bafilomycin A1, an inhibitor of endosomal acidification, significantly decreased the antifungal activity of H2K4b. This suggests that the pH-buffering and subsequent endosomal-disrupting properties of histidine-rich peptides have a role in their antifungal activity. Moreover, the ability of the histidine component of these peptides to disrupt endosomes, which allows their escape from the lysosomal pathway, may explain why these peptides are both effective antifungal agents and nucleic acid delivery carriers.

scholarly journals Common co-lipids, in synergy, impart high gene transfer properties to transfection-incompetent cationic lipids

FEBS Letters ◽  
2005 ◽  
Vol 579 (5) ◽  
pp. 1291-1300 ◽  
Author(s):  
Koushik Mukherjee ◽  
Joyeeta Sen ◽  
Arabinda Chaudhuri
Keyword(s):  
Gene Transfer ◽  
Cationic Lipids ◽  
High Gene ◽  
Transfer Properties

Head group configuration increases the biocompatibility of cationic lipids for nucleic acid delivery

2017 ◽  
Vol 5 (28) ◽  
pp. 5597-5607 ◽  
Author(s):  
Gerile Gerile ◽  
Tsogzolmaa Ganbold ◽  
Yizheng Li ◽  
Huricha Baigude
Keyword(s):  
Nucleic Acid ◽  
Therapeutic Approach ◽  
Genetic Diseases ◽  
Genetic Material ◽  
Intracellular Delivery ◽  
Cationic Lipids ◽  
Head Group ◽  
Nucleic Acid Delivery ◽  
Group Configuration

Intracellular delivery of genetic material is a potentially powerful therapeutic approach for the treatment of genetic diseases.

scholarly journals Cationic amphiphiles based on malonic acid amides as transfection mediators

2020 ◽  
Vol 15 (5) ◽  
pp. 36-45
Author(s):  
N. A. Romanova ◽  
U. A. Budanova ◽  
Yu. L. Sebyakin
Keyword(s):  
Zeta Potential ◽  
Malonic Acid ◽  
Transfection Efficiency ◽  
Cationic Lipids ◽  
Amide Bond ◽  
Resonance Spectroscopy ◽  
Carboxyl Group ◽  
Polar Head ◽  
Cationic Amphiphiles ◽  
Hydrophobic Chain

Objectives. The aim of this work is to synthesize cationic amphiphiles based on malonic acid amides. The target compounds should contain saturated and unsaturated alkyl chains in the hydrophobic portion, and one or two positive charges in the polar head as created by ethylenediamine and amino acid L-ornithine. For such cationic amphiphiles, we determined physicochemical properties and transfection efficiency of liposomes based on them.Methods. The initial compound in the synthesis is diethylmalonate. We used C-alkylation to add the first hydrophobic chain (with octylbromide, dodecylbromide, or octadecylbromide). N-oleylamine was used as the second hydrophobic chain, which was attached at the carboxyl group of the malonic acid via amide bond formation. The polar head was represented by ethylenediamine, which was then attached at the second carboxyl group of the malonic acid. Further, L-ornithine was attached to ethylenediamine to produce cationic lipids with two positive charges in the head group. The structures of the compounds were characterized by infrared spectroscopy, nuclear magnetic resonance spectroscopy, and elemental analysis. Particle size distribution was evaluated by photon correlation spectroscopy. The luciferase test was used to determine transfection efficiency using HeLa cells.Results. We have developed a synthesis scheme to produce new cationic amphiphiles with an asymmetric hydrophobic part. The obtained liposomal particles are approximately 120 nm in size and have a relatively high zeta potential of 29–30 mV.Conclusions. The size of these liposomes allows them to penetrate into cells, which makes it possible to use these compositions for transfection. The high zeta potential shows that the particles are stable. Our results demonstrate that the transfection efficiency of our liposomes (mixed with cholesterol) is comparable to a commercial formulation. Cationic amphiphiles based on malonic acid amides have great potential for liposome development for transfection.

scholarly journals Role of cationic lipids for the formulation of lipoplexes

2018 ◽  
Vol 1 (1) ◽  
pp. 1-8
Author(s):  
Varsha Singh ◽  
Pramod Kumar Sharma ◽  
Md. Aftab Alam
Keyword(s):  
Gene Therapy ◽  
Gene Transfer ◽  
Chemical Properties ◽  
Cationic Lipid ◽  
Cationic Lipids ◽  
Current Status ◽  
Viral Gene ◽  
Transfection Efficacy ◽  
Physico Chemical

Cationic lipids are widely used for their advantages over viral gene transfer as they are non-immunogenic and their production is easy. The formation of cationic liposomes to lipoplexes with the help of cationic lipids has been done. Cationic lipids are often used in combination with helper lipids such as DOPE or cholesterol for defining their structural properties. The mode of lipoplex formation has been described in this review. This review also focuses on the parameters that affects the physico-chemical properties of lipoplexes describing their use for the cationic lipid based on the gene therapy purposes. The current status and various prospects for the transfection efficacy of lipoplexes is also been described.

scholarly journals Correlation of mRNA delivery timing and protein expression in lipid-based transfection

2019 ◽  
Author(s):  
A. Reiser ◽  
D. Woschée ◽  
N. Mehrotra ◽  
R. Krzysztoń ◽  
H. H. Strey ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Protein Expression ◽  
Single Cell ◽  
Serum Protein ◽  
Transfection Efficiency ◽  
Viral Gene ◽  
Nucleic Acid Delivery ◽  
Delivery Times ◽  
Time Courses ◽  
Endosomal Release

AbstractNon-viral gene delivery is constrained by the dwell time that most synthetic nucleic acid nanocarriers spend inside endosomal compartments. In order to overcome this endosomal-release bottleneck, methods are required that measure nanocarrier uptake kinetics and transfection efficiency simultaneously. Here, we employ live-cell imaging on single-cell arrays (LISCA) to study the delivery-time distribution of lipid-based mRNA complexes under varied serum conditions. By fitting a translation-maturation model to hundreds of individual eGFP reporter fluorescence time courses, the protein expression onset times and the expression rates after transfection are determined. Using this approach, we find that delivery timing and protein expression rates are not intrinsically correlated at the single-cell level, even though population-averaged values of both parameters conjointly change as a function of increasing external serum protein fraction. Lipofectamine mediated delivery showed decreased transfection efficiency and longer delivery times with increasing serum protein concentration. This is in contrast to ionizable lipid nanoparticles (LNPs) mediated transfer, which showed increased efficiency and faster uptake in the presence of serum. In conclusion, the interdependences of single-cell expression rates and onset timing provide additional clues on uptake and release mechanisms, which are useful for improving nucleic acid delivery.

scholarly journals Viral Mimicry as a Design Template for Nucleic Acid Nanocarriers

2021 ◽  
Vol 9 ◽  
Author(s):  
Ina F. de la Fuente ◽  
Shraddha S. Sawant ◽  
Mark Q. Tolentino ◽  
Patrick M. Corrigan ◽  
Jessica L. Rouge
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Molecular Mechanisms ◽  
Transfection Efficiency ◽  
Delivery Systems ◽  
Endosomal Escape ◽  
Nucleic Acid Delivery ◽  
Metastable Structure ◽  
Oligonucleotide Delivery ◽  
Genome Protection

Therapeutic nucleic acids hold immense potential in combating undruggable, gene-based diseases owing to their high programmability and relative ease of synthesis. While the delivery of this class of therapeutics has successfully entered the clinical setting, extrahepatic targeting, endosomal escape efficiency, and subcellular localization. On the other hand, viruses serve as natural carriers of nucleic acids and have acquired a plethora of structures and mechanisms that confer remarkable transfection efficiency. Thus, understanding the structure and mechanism of viruses can guide the design of synthetic nucleic acid vectors. This review revisits relevant structural and mechanistic features of viruses as design considerations for efficient nucleic acid delivery systems. This article explores how viral ligand display and a metastable structure are central to the molecular mechanisms of attachment, entry, and viral genome release. For comparison, accounted for are details on the design and intracellular fate of existing nucleic acid carriers and nanostructures that share similar and essential features to viruses. The review, thus, highlights unifying themes of viruses and nucleic acid delivery systems such as genome protection, target specificity, and controlled release. Sophisticated viral mechanisms that are yet to be exploited in oligonucleotide delivery are also identified as they could further the development of next-generation nonviral nucleic acid vectors.

Effect of hydrophobic tails of plier-like cationic lipids on nucleic acid delivery and intracellular trafficking

2020 ◽  
Vol 573 ◽  
pp. 118798 ◽  
Author(s):  
Supusson Pengnam ◽  
Samawadee Plainwong ◽  
Prasopchai Patrojanasophon ◽  
Theerasak Rojanarata ◽  
Tanasait Ngawhirunpat ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Intracellular Trafficking ◽  
Cationic Lipids ◽  
Nucleic Acid Delivery

scholarly journals Graphene Oxide as 2D Platform for Complexation and Intracellular Delivery of siRNA

2018 ◽  
Author(s):  
Irene de Lázaro ◽  
Sandra Vranic ◽  
Domenico Marson ◽  
Artur Filipe Rodrigues ◽  
Maurizio Buggio ◽  
...  
Keyword(s):  
Graphene Oxide ◽  
Nucleic Acid ◽  
Gene Silencing ◽  
Viral Vectors ◽  
Transfection Efficiency ◽  
Unmet Need ◽  
Sharp Decrease ◽  
Intracellular Delivery ◽  
Nucleic Acid Delivery ◽  
Primary Mouse

AbstractThe development of efficient and safe nucleic acid delivery vectors remains an unmet need holding back translation of gene therapy approaches into bedside. Graphene oxide (GO) could help bypass such bottleneck thanks to its large surface area, versatile chemistry and biocompatibility, which could overall enhance transfection efficiency while abolishing some of the limitations linked to the use of viral vectors. Here, we aimed to assess the capacity of bare GO, without any further surface modification, to complex a short double-stranded nucleic acid of biological relevance (siRNA) and mediate its intracellular delivery. GO formed stable complexes with siRNA at 10:1, 20:1 and 50:1 GO:siRNA mass ratios. Complexation was further corroborated by atomistic molecular dynamics simulations. GO:siRNA complexes were promptly internalized in a primary mouse cell culture, as early as 4 h after exposure. At this time point, intracellular siRNA levels were comparable to those provided by a lipid-based transfection reagent that achieved significant gene silencing. Time-lapse tracking of internalized GO and siRNA evidenced a sharp decrease of intracellular siRNA from 4 to 12 h, while GO was sequestered in large vesicles, which may explain the lack of biological effect (i.e. gene silencing) achieved by GO:siRNA complexes. This study underlines the potential of non-surface modified GO flakes to act as 2D siRNA delivery platforms, without the need for cationic functionalization, but warrants further vector optimization to allow effective release of the nucleic acid and achieve efficient gene silencing.

Sign in / Sign up

Export Citation Format

Share Document