Efficient Gene Transfer into Mammalian Cells with Cholesteryl-Spermidine

Moradpour, Darius; Schauer, Julia I.; Zurawski, Vincent R.; Wands, Jack R.; Boutin, Raymond H.

doi:10.1006/bbrc.1996.0549

Cited by 49 publications

(33 citation statements)

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“…The head group often consists of primary, secondary or tertiary amines, but quaternary ammonium salts, guanidino and imidazole groups have also been investigated [16][17][18][19][20][21][22][23]. The most common linkers used are ethers and esters, although amides and carbamates are also employed [24][25][26]. The hydrophobic domain is generally either a double chain hydrocarbon or a cholesterol derivative.…”

Section: Cationic Lipids and Liposomes (A) -Lipidsmentioning

confidence: 99%

Structure-Activity Relationship in Cationic Lipid Mediated Gene Transfection

Niculescu‐Duvaz¹,

Heyes²,

Springer³

2003

CMC

141

112

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Non-viral synthetic vectors for gene delivery represent a safer alternative to viral vectors. Their main drawback is the low transfection efficiency, especially in vivo. Among the non-viral vectors currently in use, the cationic liposomes composed of cationic lipids are the most common. This review discusses the physicochemical properties of cationic lipids, the formation, macrostructure and specific parameters of the corresponding formulated liposomes, and the effect of all these parameters on transfection efficiency. The optimisation of liposomal vectors requires both the understanding of the biological variables involved in the transfection process, and the effect of the structural elements of the cationic lipids on these biological variables. The biological barriers relevant for in vitro and in vivo transfection are identified, and solutions to overcome them based on rational design of the cationic lipids are discussed. The review focuses on the relationship between the structure of the cationic lipid and the transfection activity. The structure is analysed in a modular manner. The hydrophobic domain, the cationic head group, the backbone that acts as a scaffold for the other domains, the linkers between backbone, hydrophobic domain and cationic head group, the polyethyleneglycol chains and the targeting moiety are identified as distinct elements of the cationic lipids used in gene therapy. The main chemical functionalities used to built these domains, as well as overall molecular features such as architecture and geometry, are presented. Studies of structure-activity relationships of each cationic lipid domain, including the authors', and the trends identified by these studies, help furthering the understanding of the mechanism governing the formation and behaviour of cationic liposomes in gene delivery, and therefore the rational design of new improved cationic lipids vectors capable of achieving clinical significance.

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Section: Cationic Lipids and Liposomes (A) -Lipidsmentioning

confidence: 99%

Structure-Activity Relationship in Cationic Lipid Mediated Gene Transfection

Niculescu‐Duvaz¹,

Heyes²,

Springer³

2003

CMC

141

112

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“…For instance, DC-Chol 3 ( Fig. 1) is one of the members of the monovalent cholesterol derivatives family (Gao and Huang 1991) and cholesterylspermidine 8 (Moradpour et al 1996) and the polyamine lipid GL67 9 (Lee et al 1996) are multivalent cholesterol vectors for gene transfer (Fig. 2).…”

Section: Cationic Lipids Derived From Cholesterolmentioning

confidence: 99%

Nature as a source of inspiration for cationic lipid synthesis

Labas

Beilvert

Barteau³

et al. 2009

Genetica

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Synthetic gene delivery systems represent an attractive alternative to viral vectors for DNA transfection. Cationic lipids are one of the most widely used non-viral vectors for the delivery of DNA into cultured cells and are easily synthesized, leading to a large variety of well-characterized molecules. This review discusses strategies for the design of efficient cationic lipids that overcome the critical barriers of in vitro transfection. A particular focus is placed on natural hydrophilic headgroups and lipophilic tails that have been used to synthesize biocompatible and non-toxic cationic lipids. We also present chemical features that have been investigated to enhance the transfection efficiency of cationic lipids by promoting the escape of lipoplexes from the endosomal compartment and DNA release from DNA-liposome complexes. Transfection efficiency studies using these strategies are likely to improve the understanding of the mechanism of cationic lipid-mediated gene delivery and to help the rational design of novel cationic lipids.

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“…Luciferase assays were performed following a standard protocol. 42 A Zeiss Axiovert photomicroscope equipped with an epifluorescence attachment was used to view cells expressing GFP. Examination by flow cytometry followed standard protocols.…”

Section: Formation Of Delivery Complexesmentioning

confidence: 99%

“…AdGFP is the replication-defective recombinant strain of the human adenovirus serotype 5 containing the GFP gene under the control of cytomegalovirus promoter and enhancer. Plasmid pCMVluc+ 42 allows expression of the firefly luciferase gene under the control of the cytomegalovirus immediate-early promoter. Plasmids were purified by two rounds of CsClgradient banding.…”

Section: Formation Of Delivery Complexesmentioning

confidence: 99%

Ligand-mediated retargeting of recombinant adenovirus for gene transfer in vivo

et al. 2000

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The development of efficient and safe methods for in vivo gene transfer is central to the success of gene therapy. Recombinant adenoviral vectors, although highly efficient, are limited by the host immune response, potential safety hazards due to obligatory cotransfer of viral proteins, and their broad tissue tropism. Here, we demonstrate in an animal model that host range and tissue tropism of a recombinant adenovirus from a distant species can be modified by complexing adenovirus with a cell-specific ligand. Thus, a

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Efficient Gene Transfer into Mammalian Cells with Cholesteryl-Spermidine

Cited by 49 publications

References 0 publications

Structure-Activity Relationship in Cationic Lipid Mediated Gene Transfection

Structure-Activity Relationship in Cationic Lipid Mediated Gene Transfection

Nature as a source of inspiration for cationic lipid synthesis

Ligand-mediated retargeting of recombinant adenovirus for gene transfer in vivo

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