Synthesis of α-amino-lipophosphonates as cationic lipids or co-lipids for DNA transfection in dendritic cells

2017 ◽  
Vol 5 (33) ◽  
pp. 6869-6881 ◽  
Author(s):  
Mathieu Berchel ◽  
Sohail Akhter ◽  
Wilfried Berthe ◽  
Cristine Gonçalves ◽  
Marine Dubuisson ◽  
...  

Cationic lipid/co-lipid combinations have been extensively explored in gene delivery as alternatives to viral vectors.

2006 ◽  
Vol 26 (4) ◽  
pp. 301-324 ◽  
Author(s):  
N. Madhusudhana Rao ◽  
Vijaya Gopal

Cationic lipids are conceptually and methodologically simple tools to deliver nucleic acids into the cells. Strategies based on cationic lipids are viable alternatives to viral vectors and are becoming increasingly popular owing to their minimal toxicity. The first-generation cationic lipids were built around the quaternary nitrogen primarily for binding and condensing DNA. A large number of lipids with variations in the hydrophobic and hydrophilic region were generated with excellent transfection efficiencies in vitro. These cationic lipids had reduced efficiencies when tested for gene delivery in vivo. Efforts in the last decade delineated the cell biological basis of the cationic lipid gene delivery to a significant detail. The application of techniques such as small angle X-ray spectroscopy (SAXS) and fluorescence microscopy, helped in linking the physical properties of lipid:DNA complex (lipoplex) with its intracellular fate. This biological knowledge has been incorporated in the design of the second-generation cationic lipids. Lipid-peptide conjugates (peptoids) are effective strategies to overcome the various cellular barriers along with the lipoplex formulations methodologies. In this context, cationic lipid-mediated gene delivery is considerably benefited by the methodologies of liposome-mediated drug delivery. Lipid mediated gene delivery has an intrinsic advantage of being a biomimetic platform on which considerable variations could be built to develop efficient in vivo gene delivery protocols.


2020 ◽  
Vol 27 (8) ◽  
pp. 698-710
Author(s):  
Roya Cheraghi ◽  
Mahboobeh Nazari ◽  
Mohsen Alipour ◽  
Saman Hosseinkhani

Gene-based therapy largely relies on the vector type that allows a selective and efficient transfection into the target cells with maximum efficacy and minimal toxicity. Although, genes delivered utilizing modified viruses transfect efficiently and precisely, these vectors can cause severe immunological responses and are potentially carcinogenic. A promising method of overcoming this limitation is the use of non-viral vectors, including cationic lipids, polymers, dendrimers, and peptides, which offer potential routes for compacting DNA for targeted delivery. Although non-viral vectors exhibit reduced transfection efficiency compared to their viral counterpart, their superior biocompatibility, non-immunogenicity and potential for large-scale production make them increasingly attractive for modern therapy. There has been a great deal of interest in the development of biomimetic chimeric peptides. Biomimetic chimeric peptides contain different motifs for gene translocation into the nucleus of the desired cells. They have motifs for gene targeting into the desired cell, condense DNA into nanosize particles, translocate the gene into the nucleus and enhance the release of the particle into the cytoplasm. These carriers were developed in recent years. This review highlights the stepwise development of the biomimetic chimeric peptides currently being used in gene 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 ◽  
...  

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


COSMOS ◽  
2014 ◽  
Vol 10 (01) ◽  
pp. 25-38 ◽  
Author(s):  
AMELIA LI MIN TAN ◽  
ALISA XUE LING LIM ◽  
YITING ZHU ◽  
YI YAN YANG ◽  
MAJAD KHAN

Advances in medical research have shed light on the genetic cause of many human diseases. Gene therapy is a promising approach which can be used to deliver therapeutic genes to treat genetic diseases at its most fundamental level. In general, nonviral vectors are preferred due to reduced risk of immune response, but they are also commonly associated with low transfection efficiency and high cytotoxicity. In contrast to viral vectors, nonviral vectors do not have a natural mechanism to overcome extra- and intracellular barriers when delivering the therapeutic gene into cell. Hence, its design has been increasingly complex to meet challenges faced in targeting of, penetration of and expression in a specific host cell in achieving more satisfactory transfection efficiency. Flexibility in design of the vector is desirable, to enable a careful and controlled manipulation of its properties and functions. This can be met by the use of bolaamphiphile, a special class of lipid. Unlike conventional lipids, bolaamphiphiles can form asymmetric complexes with the therapeutic gene. The advantage of having an asymmetric complex lies in the different purposes served by the interior and exterior of the complex. More effective gene encapsulation within the interior of the complex can be achieved without triggering greater aggregation of serum proteins with the exterior, potentially overcoming one of the great hurdles faced by conventional single-head cationic lipids. In this review, we will look into the physiochemical considerations as well as the biological aspects of a bolaamphiphile-based gene delivery system.


2019 ◽  
Vol 7 (1) ◽  
pp. 149-158 ◽  
Author(s):  
Laila Kudsiova ◽  
Atefeh Mohammadi ◽  
M. Firouz Mohd Mustapa ◽  
Frederick Campbell ◽  
Katharina Welser ◽  
...  

Lipoplexes (LDs) have been prepared from DNA, DOPE and either a dichain oxyethylated cationic lipid or their novel trichain (TC) counterpart.


2015 ◽  
Vol 3 (1) ◽  
pp. 119-126 ◽  
Author(s):  
Yinan Zhao ◽  
Shubiao Zhang ◽  
Yuan Zhang ◽  
Shaohui Cui ◽  
Huiying Chen ◽  
...  

A novel tri-peptide cationic lipid can efficiently transfer DNA and siRNA into tumor cells and tumors of mice with little in vitro and in vivo toxicity.


Author(s):  
Rohan Aggarwal ◽  
Monika Targhotra ◽  
Bhumika Kumar ◽  
P.K Sahoo ◽  
Meenakshi K Chauhan

In the past few years gene delivery system has gained a huge attention owing to its proved efficacy in several diseases especially in those caused by genetic and/oroncological malfunctioning. The effective gene delivery mainly depends on the carrier molecules that can ensure the safe and specific delivery of the nucleic acidmolecules. Viral vectors have been used for a longer period as the gene transfer vehicle. However, these viral vectors have potential immunological disadvantages that made them less preferred. Recently, non-viral vectors such as polyplexes have emerged as a promising alternative for viral vectors. Polyplexes are formed by conjugating a polymer with DNA and in maximum cases the cationic polymers are preferred over others. The structure and stability of the polyplexes depends on various factors. The ability of the polymer to condense the DNA mainly dictates the efficiency of the polyplex mediated transfection. In this review we are going to provide a framework for the synthesis and design of the polyplexes along with the structure and stability of the complexes pertaining to mechanism of action, characterization and therapeutic application, including polyethyleneimine mediated cytotoxicity as well as newer strategies for the generation of better polyplexes.


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