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 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 In Situ Loading and Delivery of Short Single- and Double-Stranded DNA by Supramolecular Organic Frameworks

CCS Chemistry ◽  
2019 ◽  
Vol 1 (2) ◽  
pp. 156-165 ◽  
Author(s):  
Bo Yang ◽  
Xiao-Dan Zhang ◽  
Jian Li ◽  
Jia Tian ◽  
Yi-Peng Wu ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Dna Sequences ◽  
Laser Scanning ◽  
High Stability ◽  
Intracellular Delivery ◽  
Water Soluble ◽  
Laser Scanning Microscopy ◽  
Confocal Laser ◽  
Nucleic Acid Delivery

Short DNA represents an important class of biomacromolecules that are widely applied in gene therapy, editing, and modulation. However, the development of simple and reliable methods for their intracellular delivery remains a challenge. Herein, we describe that seven water-soluble, homogeneous supramolecular organic frameworks (SOFs) with a well-defined pore size and high stability in water that can accomplish in situ inclusion of single-stranded (ss) and double-stranded (ds) DNA (21, 23, and 58 nt) and effective intracellular delivery (including two noncancerous and six cancerous cell lines). Fluorescence quenching experiments for single and double end-labeled ss- and ds-DNA support that the DNA sequences can be completely enveloped by the SOFs. Confocal laser scanning microscopy and flow cytometry reveal that five of the SOFs exhibit excellent delivery efficiencies that, in most of the studied cases, outperform the commercial standard Lipo2000, even at low SOF–nucleic acid ratios. In addition to high delivery efficiencies, the water-soluble, self-assembled SOF carriers have a variety of advantages, including convenient preparation, high stability, and in situ DNA inclusion, which are all critical for practical applications in nucleic acid delivery.

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.

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.

Asymmetric cationic lipid based non-viral vectors for an efficient nucleic acid delivery

RSC Advances ◽  
2016 ◽  
Vol 6 (81) ◽  
pp. 77841-77848 ◽  
Author(s):  
Rakeshchandra R. Meka ◽  
Sudhakar Godeshala ◽  
Srujan Marepally ◽  
Ketan Thorat ◽  
Hari Krishna Reddy Rachamalla ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Viral Vectors ◽  
Cationic Lipid ◽  
Cationic Lipids ◽  
Nucleic Acid Delivery

Cationic lipids have been extensively studied for their ability to complex with nucleic acids to condense and consequently deliver them into the cells.

scholarly journals Cardiolipin-Based Lipopolyplex Platform for the Delivery of Diverse Nucleic Acids into Gram-Negative Bacteria

2019 ◽  
Vol 12 (2) ◽  
pp. 81 ◽  
Author(s):  
Federico Perche ◽  
Tony Le Gall ◽  
Tristan Montier ◽  
Chantal Pichon ◽  
Jean-Marc Malinge
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Essential Gene ◽  
Bacterial Species ◽  
Intracellular Delivery ◽  
Bactericidal Effect ◽  
Health Concern ◽  
Nucleic Acid Delivery ◽  
Gram Negative Bacteria ◽  
Gram Negative

Antibiotic resistance is a growing public health concern. Because only a few novel classes of antibiotics have been developed in the last 40 years, such as the class of oxazolidinones, new antibacterial strategies are urgently needed (Coates, A.R. et al., 2011). Nucleic acid-based antibiotics are a new type of antimicrobials. However, free nucleic acids cannot spontaneously cross the bacterial cell wall and membrane; consequently, their intracellular delivery into bacteria needs to be assisted. Here, we introduce an original lipopolyplex system named liposome polymer nucleic acid (LPN), capable of versatile nucleic acid delivery into bacteria. We characterized LPN formed with significant therapeutic nucleic acids: 11 nt antisense single-stranded (ss) DNA and double-stranded (ds) DNA of 15 and 95 base pairs (bp), 9 kbp plasmid DNA (pDNA), and 1000 nt ssRNA. All these complexes were efficiently internalized by two different bacterial species, i.e., Escherichia coli and Pseudomonas aeruginosa, as shown by flow cytometry. Consistent with intracellular delivery, LPN prepared with an antisense oligonucleotide and directed against an essential gene, induced specific and important bacterial growth inhibition likely leading to a bactericidal effect. Our findings indicate that LPN is a versatile platform for efficient delivery of diverse nucleic acids into Gram-negative bacteria.

scholarly journals Transgene expression in mice of the Opa1 mitochondrial transmembrane protein through bicontinuous cubic lipoplexes containing gemini imidazolium surfactants

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Mónica Muñoz-Úbeda ◽  
Martina Semenzato ◽  
Anais Franco-Romero ◽  
Elena Junquera ◽  
Emilio Aicart ◽  
...  
Keyword(s):  
Transgene Expression ◽  
Transmembrane Protein ◽  
Quantitative Polymerase Chain Reaction ◽  
Genetic Material ◽  
Cationic Lipids ◽  
Head Group ◽  
Polar Head ◽  
Cubic Phases ◽  
Head Groups ◽  
Bicontinuous Cubic

Abstract Background Lipoplexes are non-viral vectors based on cationic lipids used to deliver DNA into cells, also known as lipofection. The positively charge of the hydrophilic head-group provides the cationic lipids the ability to condensate the negatively charged DNA into structured complexes. The polar head can carry a large variety of chemical groups including amines as well as guanidino or imidazole groups. In particular, gemini cationic lipids consist of two positive polar heads linked by a spacer with different length. As for the hydrophobic aliphatic chains, they can be unsaturated or saturated and are connected to the polar head-groups. Many other chemical components can be included in the formulation of lipoplexes to improve their transfection efficiency, which often relies on their structural features. Varying these components can drastically change the arrangement of DNA molecules within the lamellar, hexagonal or cubic phases that are provided by the lipid matrix. Lipofection is widely used to deliver genetic material in cell culture experiments but the simpler formulations exhibit major drawbacks related to low transfection, low specificity, low circulation half-life and toxicity when scaled up to in vivo experiments. Results So far, we have explored in cell cultures the transfection ability of lipoplexes based on gemini cationic lipids that consist of two C16 alkyl chains and two imidazolium polar head-groups linked with a polyoxyethylene spacer, (C16Im)2(C4O). Here, PEGylated lipids have been introduced to the lipoplex formulation and the transgene expression of the Opa1 mitochondrial transmembrane protein in mice was assessed. The addition of PEG on the surface of the lipid mixed resulted in the formation of Ia3d bicontinuous cubic phases as determined by small angle X-ray scattering. After a single intramuscular administration, the cubic lipoplexes were accumulated in tissues with tight endothelial barriers such as brain, heart, and lungs for at least 48 h. The transgene expression of Opa1 in those organs was identified by western blotting or RNA expression analysis through quantitative polymerase chain reaction. Conclusions The expression reported here is sufficient in magnitude, duration and toxicity to consolidate the bicontinuous cubic structures formed by (C16Im)2(C4O)-based lipoplexes as valuable therapeutic agents in the field of gene delivery. Graphical Abstract

Non-Viral Nucleic Acid Delivery: Key Challenges and Future Directions

2011 ◽  
Vol 8 (3) ◽  
pp. 235-244 ◽  
Author(s):  
Mahmoud Elsabahy ◽  
Adil Nazarali ◽  
Marianna Foldvari
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acid Delivery ◽  
Viral Nucleic Acid ◽  
Future Directions
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