Deciphering the response of asymmetry in the hydrophobic chains of novel cationic lipids towards biological function

2020 ◽  
Vol 22 (3) ◽  
pp. 1738-1746 ◽  
Author(s):  
Dipanjan Mukherjee ◽  
Priya Singh ◽  
Tatini Rakshit ◽  
Theja P. Puthiya-Purayil ◽  
Praveen Kumar Vemula ◽  
...  
Keyword(s):  
Nucleic Acids ◽  
Biological Function ◽  
Cationic Liposome ◽  
Cationic Lipids ◽  
Cell Transfection ◽  
Molecular Architecture

Variations in molecular architecture of the hydrophobic tails of cationic lipids influence cationic liposome*s efficiency of delivering nucleic acids during cell transfection.

An injectable paste of calcium phosphate nanorods, functionalized with nucleic acids, for cell transfection and gene silencing

2010 ◽  
Vol 20 (29) ◽  
pp. 6144 ◽  
Author(s):  
J. Klesing ◽  
S. Chernousova ◽  
A. Kovtun ◽  
S. Neumann ◽  
L. Ruiz ◽  
...  
Keyword(s):  
Calcium Phosphate ◽  
Nucleic Acids ◽  
Gene Silencing ◽  
Cell Transfection

scholarly journals Сationic liposomes as delivery systems for nucleic acids

2020 ◽  
Vol 15 (1) ◽  
pp. 7-27
Author(s):  
A. A. Mikheev ◽  
E. V. Shmendel ◽  
E. S. Zhestovskaya ◽  
G. V. Nazarov ◽  
M. A. Maslov
Keyword(s):  
Gene Therapy ◽  
Nucleic Acids ◽  
Serum Proteins ◽  
Transfection Efficiency ◽  
Biological Fluids ◽  
Genetic Material ◽  
Cationic Liposomes ◽  
Delivery Systems ◽  
Cationic Lipids

Objectives. Gene therapy is based on the introduction of genetic material into cells, tissues, or organs for the treatment of hereditary or acquired diseases. A key factor in the success of gene therapy is the development of delivery systems that can efficiently transfer genetic material to the place of their therapeutic action without causing any associated side effects. Over the past 10 years, significant effort has been directed toward creating more efficient and biocompatible vectors capable of transferring nucleic acids (NAs) into cells without inducing an immune response. Cationic liposomes are among the most versatile tools for delivering NAs into cells; however, the use of liposomes for gene therapy is limited by their low specificity. This is due to the presence of various biological barriers to the complex of liposomes with NA, including instability in biological fluids, interaction with serum proteins, plasma and nuclear membranes, and endosomal degradation. This review summarizes the results of research in recent years on the development of cationic liposomes that are effective in vitro and in vivo. Particular attention is paid to the individual structural elements of cationic liposomes that determine the transfection efficiency and cytotoxicity. The purpose of this review was to provide a theoretical justification of the most promising choice of cationic liposomes for the delivery of NAs into eukaryotic cells and study the effect of the composition of cationic lipids (CLs) on the transfection efficiency in vitro.Results. As a result of the analysis of the related literature, it can be argued that one of the most promising delivery systems of NAs is CL based on cholesterol and spermine with the addition of a helper lipid DOPE. In addition, it was found that varying the composition of cationic liposomes, the ratio of CL to NA, or the size and zeta potential of liposomes has a significant effect on the transfection efficiency.Conclusions. Further studies in this direction should include optimization of the conditions for obtaining cationic liposomes, taking into account the physicochemical properties and established laws. It is necessary to identify mechanisms that increase the efficiency of NA delivery in vitro by searching for optimal structures of cationic liposomes, determining the ratio of lipoplex components, and studying the delivery efficiency and properties of multicomponent liposomes.

Gene therapy promises accurate, targeted administration and overcoming drug resistance in diverse cancer cells

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Gene Therapy ◽  
Drug Resistance ◽  
Nucleic Acid ◽  
Nucleic Acids ◽  
Clinical Research ◽  
Cancer Cells ◽  
Cationic Lipids ◽  
Target Cells ◽  
Genetic Components ◽  
Wide Range

Nucleic acid-based therapeutics such as siRNA and miRNA employ the silencing capabilities of the RNAi mechanism to affect the expression of one gene or several genes in target cells. Nucleic acid-based therapies enable accurate, targeted administration and overcoming drug resistance in diverse cancer cells. Several studies have shown that they can be utilized alongside pharmacological therapy to increase the efficacy of existing therapies. In addition, nucleic acid-based therapies have the potential to widen the spectrum of druggable targets for a range of diseases and emerge as a novel therapeutic technique for treating a number of diseases that are today untreatable. Nucleic acids are dependent on their effective distribution to target cells, which need correct complexation and encapsulation in a delivery mechanism. Although nucleic acids exist in a variety of forms and sizes, their physical and chemical commonality allow them to be loaded into a wide range of delivery vehicles. The primary biomaterials used to encapsulate genetic components were cationic lipids and polymers. Furthermore, the experiments focused particularly on effective transfection in target cells.Recent breakthroughs in NP-based RNA therapeutics have spurred a flood of clinical research, facing many challenges. In vivo, pharmacokinetics of different RNA-based medications must be researched to establish the viability and therapeutic potential of nucleic acid-based therapeutics. The U.S. Food and Drug Administration recently authorized many NP-based gene therapy. In 2019, Novartis authorized Zolgensma (onasemnogene abeparvovec-xioi) to treat spinal muscle atrophy. The first clinical research employing siRNA began in 2004 and is considered a milestone in nucleic acid-based drug development. Thirty clinical investigations have subsequently been completed. In 2018, the US FDA cleared Onpattro (Patisiran, Alnylam Pharmaceuticals) for the treatment of polyneuropathy caused by transthyretin amyloidosis.Several new generations of nucleic acid compositions employing polymer nanoparticles or liposomes are presently undergoing clinical testing. If allowed, the debut of nucleic acid-based treatments would represent a watershed event in immunotherapy. Advances in the design and development of biocompatible nanomaterials would allow us to overcome the above-mentioned problems and so show the potential to deliver nucleic acids in the treatment of a number of illnesses.

Cross-linked nucleic acids: Formation, structure, and biological function

2010 ◽  
Vol 36 (1) ◽  
pp. 49-72 ◽  
Author(s):  
V. A. Efimov ◽  
S. V. Fedyunin ◽  
O. G. Chakhmakhcheva
Keyword(s):  
Nucleic Acids ◽  
Biological Function

Optimization on cationic liposome-mediated cell transfection of plasmid DNA

2011 ◽  
Vol 10 (5) ◽  
pp. 290-292
Author(s):  
Mingang Ying ◽  
Changhua Zhuo ◽  
Weidong Zang
Keyword(s):  
Plasmid Dna ◽  
Cationic Liposome ◽  
Cell Transfection

scholarly journals Resveratrol Enhances mRNA and siRNA Lipid Nanoparticles Primary CLL Cell Transfection

Pharmaceutics ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 520
Author(s):  
Edo Kon ◽  
Inbal Hazan-Halevy ◽  
Daniel Rosenblum ◽  
Niv Cohen ◽  
Sushmita Chatterjee ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Nucleic Acids ◽  
Caffeic Acid ◽  
Targeted Therapies ◽  
Lipid Nanoparticles ◽  
Lymphocytic Leukemia ◽  
Cell Transfection ◽  
Formidable Challenge ◽  
Patient Heterogeneity ◽  
Adult Leukemia

Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in Western populations. Therapies such as mRNA and siRNA encapsulated in lipid nanoparticles (LNPs) represent a clinically advanced platform and are utilized for a wide variety of applications. Unfortunately, transfection of RNA into CLL cells remains a formidable challenge and a bottleneck for developing targeted therapies for this disease. Therefore, we aimed to elucidate the barriers to efficient transfection of RNA-encapsulated LNPs into primary CLL cells to advance therapies in the future. To this end, we transfected primary CLL patient samples with mRNA and siRNA payloads encapsulated in an FDA-approved LNP formulation and characterized the transfection. Additionally, we tested the potential of repurposing caffeic acid, curcumin and resveratrol to enhance the transfection of nucleic acids into CLL cells. The results demonstrate that the rapid uptake of LNPs is required for successful transfection. Furthermore, we demonstrate that resveratrol enhances the delivery of both mRNA and siRNA encapsulated in LNPs into primary CLL patient samples, overcoming inter-patient heterogeneity. This study points out the important challenges to consider for efficient RNA therapeutics for CLL patients and advocates the use of resveratrol in combination with RNA lipid nanoparticles to enhance delivery into CLL cells.

The Bakerian Lecture: Molecular structure in the polysaccharide group

1959 ◽  
Vol 252 (1270) ◽  
pp. 287-312 ◽  
Keyword(s):  
Molecular Structure ◽  
Fine Structure ◽  
Biological Function ◽  
Structural Features ◽  
Molecular Structures ◽  
Molecular Architecture ◽  
Considerable Time ◽  
General Acceptance ◽  
Naturally Occurring ◽  
Precise Knowledge

It has been clear for some considerable time that a more precise knowledge of the molecular structure of the polysaccharides is needed for the solution of many problems in biology and medicine. This was emphasized by Sir Norman Haworth in the Bakerian Lecture delivered in 1944, when he reviewed the position then reached concerning the structure, biological function and synthesis of typical polysaccharides. In this connexion it is of interest to recall that by 1944 the view that naturally occurring colloidal substances such as starch and cellulose possessed molecular structures held together by normal co-valent bonds had received general acceptance for less than 20 years. Furthermore, the evidence for the main structural features of the polysaccharides had been acquired by difficult and laborious experimental methods which normally involved the manipulation of large quantities of material. Some idea of the general molecular architecture of many polysaccharides had been gained, but the methods then available were not capable of delving much deeper into the detailed structural features. This fine structure is nevertheless of particular importance, since the presence of irregular features in the molecule, even in slight degree, may alter quite markedly the behaviour of these high polymers. It will be readily understood also that the fine structure of these macromolecules is a matter of great moment in enzymology.

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