How cationic lipids transfer nucleic acids into cells and across cellular membranes: Recent advances

2013 ◽  
Vol 166 (1) ◽  
pp. 46-56 ◽  
Author(s):  
Zia ur Rehman ◽  
Inge S. Zuhorn ◽  
Dick Hoekstra
2012 ◽  
Vol 19 (6) ◽  
pp. 462-468 ◽  
Author(s):  
Nancy Bo Yin Tsui ◽  
Yuk Ming Dennis Lo

Author(s):  
A. A. Mikheev ◽  
E. V. Shmendel ◽  
E. S. Zhestovskaya ◽  
G. V. Nazarov ◽  
M. A. Maslov

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.


2021 ◽  
Author(s):  
Moataz Dowaidar

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.


2018 ◽  
Vol 6 (3) ◽  
pp. 438-451 ◽  
Author(s):  
Yuwei Zhu ◽  
Zhiwei Huang

Abstract Clustered regularly interspaced short palindromic repeats (CRISPR) and accompanying CRISPR-associated (Cas) proteins provide RNA-guided adaptive immunity for prokaryotes to defend themselves against viruses. The CRISPR-Cas systems have attracted much attention in recent years for their power in aiding the development of genome editing tools. Based on the composition of the CRISPR RNA-effector complex, the CRISPR-Cas systems can be divided into two classes and six types. In this review, we summarize recent advances in the structural biology of the CRISPR-Cas-mediated genome editing tools, which helps us to understand the mechanism of how the guide RNAs assemble with diverse Cas proteins to cleave target nucleic acids.


2020 ◽  
Vol 22 (3) ◽  
pp. 1738-1746 ◽  
Author(s):  
Dipanjan Mukherjee ◽  
Priya Singh ◽  
Tatini Rakshit ◽  
Theja P. Puthiya-Purayil ◽  
Praveen Kumar Vemula ◽  
...  

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


2014 ◽  
Vol 2 (46) ◽  
pp. 8069-8084 ◽  
Author(s):  
Amit Singh ◽  
Meghna Talekar ◽  
Thanh-Huyen Tran ◽  
Abishek Samanta ◽  
Ravi Sundaram ◽  
...  

This update summarizes the recent advances in combinatorial design of polymeric material for developing multifunctional nanovectors to deliver nucleic acids and chemodrugs for cancer therapy.


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Jin Lin ◽  
Jing Li ◽  
Bo Huang ◽  
Jing Liu ◽  
Xin Chen ◽  
...  

Exosomes are 30–120 nm endocytic membrane-derived vesicles that participate in cell-to-cell communication and protein and RNA delivery. Exosomes harbor a variety of proteins, nucleic acids, and lipids and are present in many and perhaps all bodily fluids. A significant body of literature has demonstrated that molecular constituents of exosomes, especially exosomal proteins and microRNAs (miRNAs), hold great promise as novel biomarkers for clinical diagnosis. In this minireview, we summarize recent advances in the research of exosomal biomarkers and their potential application in clinical diagnostics. We also provide a brief overview of the formation, function, and isolation of exosomes.


The Analyst ◽  
2009 ◽  
Vol 134 (7) ◽  
pp. 1265 ◽  
Author(s):  
Michael Towrie ◽  
Gerard W. Doorley ◽  
Michael W. George ◽  
Anthony W. Parker ◽  
Susan J. Quinn ◽  
...  

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