Gene delivery by cationic lipids: in and out of an endosome

2007 ◽  
Vol 35 (1) ◽  
pp. 68-71 ◽  
Author(s):  
D. Hoekstra ◽  
J. Rejman ◽  
L. Wasungu ◽  
F. Shi ◽  
I. Zuhorn
Keyword(s):  
Gene Delivery ◽  
Molecular Mechanisms ◽  
Transfection Efficiency ◽  
Cationic Lipids ◽  
Phase Changes ◽  
Model Systems ◽  
Major Pathway ◽  
Intracellular Lipids ◽  
Relative Contribution ◽  
Endosomal Membranes

Cationic lipids are exploited as vectors (‘lipoplexes’) for delivering nucleic acids, including genes, into cells for both therapeutic and cell biological purposes. However, to meet therapeutic requirements, their efficacy needs major improvement, and better defining the mechanism of entry in relation to eventual transfection efficiency could be part of such a strategy. Endocytosis is the major pathway of entry, but the relative contribution of distinct endocytic pathways, including clathrin- and caveolae-mediated endocytosis and/or macropinocytosis is as yet poorly defined. Escape of DNA/RNA from endosomal compartments is thought to represent a major obstacle. Evidence is accumulating that non-lamellar phase changes of the lipoplexes, facilitated by intracellular lipids, which allow DNA to dissociate from the vector and destabilize endosomal membranes, are instrumental in plasmid translocation into the cytosol, a prerequisite for nuclear delivery. To further clarify molecular mechanisms and to appreciate and overcome intracellular hurdles in lipoplex-mediated gene delivery, quantification of distinct steps in overall transfection and proper model systems are required.

Stepwise Development of Biomimetic Chimeric Peptides for Gene Delivery

2020 ◽  
Vol 27 (8) ◽  
pp. 698-710
Author(s):  
Roya Cheraghi ◽  
Mahboobeh Nazari ◽  
Mohsen Alipour ◽  
Saman Hosseinkhani
Keyword(s):  
Gene Delivery ◽  
Targeted Delivery ◽  
Viral Vectors ◽  
Large Scale ◽  
Transfection Efficiency ◽  
Cationic Lipids ◽  
Target Cells ◽  
Scale Production ◽  
Stepwise Development ◽  
Chimeric Peptides

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.

scholarly journals Competitive binding and molecular crowding regulate the cytoplasmic interactome of non-viral polymeric gene delivery vectors

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Aji Alex M. Raynold ◽  
Danyang Li ◽  
Lan Chang ◽  
Julien E. Gautrot
Keyword(s):  
Gene Delivery ◽  
Molecular Mechanisms ◽  
Transfection Efficiency ◽  
Competitive Binding ◽  
Molecular Crowding ◽  
Gene Delivery Vectors ◽  
Polymeric Gene Delivery ◽  
Associated Proteins ◽  
Improved Design

AbstractIn contrast to the processes controlling the complexation, targeting and uptake of polycationic gene delivery vectors, the molecular mechanisms regulating their cytoplasmic dissociation remains poorly understood. Upon cytosolic entry, vectors become exposed to a complex, concentrated mixture of molecules and biomacromolecules. In this report, we characterise the cytoplasmic interactome associated with polycationic vectors based on poly(dimethylaminoethyl methacrylate) (PDMAEMA) and poly(2-methacrylolyloxyethyltrimethylammonium chloride) (PMETAC) brushes. To quantify the contribution of different classes of low molar mass molecules and biomacromolecules to RNA release, we develop a kinetics model based on competitive binding. Our results identify the importance of competition from highly charged biomacromolecules, such as cytosolic RNA, as a primary regulator of RNA release. Importantly, our data indicate the presence of ribosome associated proteins, proteins associated with translation and transcription factors that may underly a broader impact of polycationic vectors on translation. In addition, we bring evidence that molecular crowding modulates competitive binding and demonstrate how the modulation of such interactions, for example via quaternisation or the design of charge-shifting moieties, impacts on the long-term transfection efficiency of polycationic vectors. Understanding the mechanism regulating cytosolic dissociation will enable the improved design of cationic vectors for long term gene release and therapeutic efficacy.

Amphiphilic polymers formed from ring-opening polymerization: a strategy for the enhancement of gene delivery

2017 ◽  
Vol 5 (4) ◽  
pp. 718-729 ◽  
Author(s):  
Yi-Mei Zhang ◽  
Zheng Huang ◽  
Ji Zhang ◽  
Wan-Xia Wu ◽  
Yan-Hong Liu ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Ring Opening ◽  
Transfection Efficiency ◽  
Ring Opening Polymerization ◽  
Amphiphilic Polymers ◽  
Cationic Lipids ◽  
Promising Strategy

Ring-opening polymerization was found to be a promising strategy to improve the transfection efficiency and serum tolerance of cationic lipids.

scholarly journals Niosomes based on synthetic cationic lipids for gene delivery: the influence of polar head-groups on the transfection efficiency in HEK-293, ARPE-19 and MSC-D1 cells

2015 ◽  
Vol 13 (4) ◽  
pp. 1068-1081 ◽  
Author(s):  
E. Ojeda ◽  
G. Puras ◽  
M. Agirre ◽  
J. Zárate ◽  
S. Grijalvo ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Transfection Efficiency ◽  
Cationic Lipids ◽  
Head Group ◽  
Polar Head Group ◽  
Hek 293 ◽  
Polar Head ◽  
Head Groups

We designed niosomes based on three lipids that differed only in the polar-head group to analyze their influence on the transfection efficiency.

CATIONIC BOLAAMPHIPHILES FOR GENE DELIVERY

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
Keyword(s):  
Gene Delivery ◽  
Viral Vectors ◽  
Serum Proteins ◽  
Transfection Efficiency ◽  
Genetic Diseases ◽  
Cationic Lipids ◽  
Nonviral Vectors ◽  
Therapeutic Gene ◽  
Natural Mechanism ◽  
High Cytotoxicity

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.

Efficient Gene Delivery Using Anionic Liposome-Complexed Polyplexes (LPDII)

2000 ◽  
Vol 20 (5) ◽  
pp. 419-432 ◽  
Author(s):  
Wenjin Guo ◽  
Robert J. Lee
Keyword(s):  
Gene Delivery ◽  
Mammalian Cells ◽  
High Efficiency ◽  
Transfection Efficiency ◽  
Cationic Lipids ◽  
Luciferase Reporter ◽  
Luciferase Reporter Gene ◽  
Efficient Gene ◽  
Anionic Liposomes ◽  
Cholesteryl Hemisuccinate

Synthetic gene transfer vectors based on polyplexes complexed to anionic liposomes (LPDII vectors) were characterized for their transfection efficiency in cultured mammalian cells. The effects of polycation to DNA ratio, lipid to DNA ratio, choice of polycation and lipid composition were systematically evaluated in human oral carcinoma KB cells, using a luciferase reporter gene. For LPDII formulations containing poly-L-lysine and dioeoylphosphatidylethanolamine/cholesteryl hemisuccinate (DOPE/CHEMS) anionic liposomes, at a constant lipid to DNA ratio, an increase in the polycation/DNA (N/P) ratio resulted in an increase in transfection activity. Meanwhile, the optimal lipid to DNA ratio for efficient gene delivery was influenced by the N/P ratio used, and was increased at higher N/P ratios. For the DNA condensing agent, poly-L-lysine could be replaced by polyethylenimine (PEI) as the DNA condensing agent in the formulations. For the lipidic components, CHEMS could be replaced by other anioniclipids including oleic acid, dicetylphosphate and phosphatidylserine, but DOPE, a fusogenic helper lipid, could not be replaced by dioleolyphosphatidylcholine. LPDII formulation showed significantly less cytotoxicity compared to the commonly used cationic lipsomes or PEI mediated transfection and several cell lines were transfected with high efficiency. LPDII vectors avoid the use of toxic cationic lipids and may have potential application in gene therapy.

Microfluidic manufacturing of surface-functionalized graphene oxide nanoflakes for gene delivery

Nanoscale ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 2733-2741 ◽  
Author(s):  
Riccardo Di Santo ◽  
Luca Digiacomo ◽  
Sara Palchetti ◽  
Valentina Palmieri ◽  
Giordano Perini ◽  
...  
Keyword(s):  
Graphene Oxide ◽  
Gene Delivery ◽  
Transfection Efficiency ◽  
Cationic Lipids ◽  
Hybrid Nanoparticles ◽  
Functionalized Graphene ◽  
Functionalized Graphene Oxide ◽  
Microfluidic Assembly

Microfluidic assembly of graphene oxide nanoflakes and cationic lipids produces surface functionalized hybrid nanoparticles with superior transfection efficiency and no cytotoxicity.

Transfection Efficiency of Cationic Lipids with Different Hydrophobic Domains in Gene Delivery

2010 ◽  
Vol 21 (4) ◽  
pp. 563-577 ◽  
Author(s):  
DeFu Zhi ◽  
ShuBiao Zhang ◽  
Bing Wang ◽  
YiNan Zhao ◽  
BaoLing Yang ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Transfection Efficiency ◽  
Cationic Lipids

Pyridinium cationic lipids in gene delivery: an in vitro and in vivo comparison of transfection efficiency versus a tetraalkylammonium congener

2005 ◽  
Vol 435 (1) ◽  
pp. 217-226 ◽  
Author(s):  
Marc A. Ilies ◽  
Betty H. Johnson ◽  
Fred Makori ◽  
Aaron Miller ◽  
William A. Seitz ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Transfection Efficiency ◽  
Cationic Lipids

New multivalent cationic lipids reveal bell curve for transfection efficiency versus membrane charge density: lipid-DNA complexes for gene delivery

2005 ◽  
Vol 7 (6) ◽  
pp. 739-748 ◽  
Author(s):  
Ayesha Ahmad ◽  
Heather M. Evans ◽  
Kai Ewert ◽  
Cyril X. George ◽  
Charles E. Samuel ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Charge Density ◽  
Transfection Efficiency ◽  
Cationic Lipids ◽  
Dna Complexes ◽  
Bell Curve ◽  
Membrane Charge
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