Cationic Lipophosphoramidates and Lipophosphoguanidines Are Very Efficient for in Vivo DNA Delivery

Picquet, E.; Ny, Karine Le; Delépine, Pascal; Montier, Tristan; Yaouanc, Jean‐Jacques; Cartier, Dominique; Abbayes, Hervé des; Férec, Claude; Clément, Jean-Claude

doi:10.1021/bc050097k

Cited by 60 publications

(64 citation statements)

References 13 publications

(3 reference statements)

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“…Solvents were freshly distilled on appropriate drying agents (CH 2 Cl 2 was distilled over P 2 O 5 , DIPEA was distilled over NaOH), and reactions were run under nitrogen. All compounds were fully characterised by 1 H (500 MHz), 13 C (100 MHz) and 31 P (121.49 MHz) NMR spectroscopy (Bruker AC 300 and Advance DRX 500 spectrometers). Coupling constants (J) are given in Hertz.…”

Section: Methodsmentioning

confidence: 99%

“…Coupling constants (J) are given in Hertz. When needed, 13 C heteronuclear HMQC and HMBC were used to establish structures unambiguously. Mass spectroscopy analyses were performed by CRMPO (UniversitØ de Rennes 1, Rennes, France) with a MS/MS high-resolution Micromass ZABSpec-TOF.…”

Section: Methodsmentioning

confidence: 99%

“…These cationic phosphoramidate lipids proved to be efficient in in vitro and in vivo transfection experiments. [13,14,15] In this series of vectors, one of the most efficient (in term of high transfection efficiency and low toxicity) was KLN47 (Scheme 1). These promising results encouraged us to investigate some new structural modifications of phosphoramidate lipids and to evalIn an effort to enhance the gene-transfer efficiencies of cationic lipids and to decrease their toxicities, a series of new phosphoramidate lipids with chemical similarity to cell membrane phospholipids was synthesised.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis and Transfection Activity of New Cationic Phosphoramidate Lipids: High Efficiency of an Imidazolium Derivative

Mével¹,

Breuzard²,

Yaouanc³

et al. 2008

ChemBioChem

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In an effort to enhance the gene-transfer efficiencies of cationic lipids and to decrease their toxicities, a series of new phosphoramidate lipids with chemical similarity to cell membrane phospholipids was synthesised. These lipids contained various cationic headgroups, such as arginine methyl ester, lysine methyl ester, homoarginine methyl ester, ethylenediamine, diaminopropane, guanidinium and imidazolium. Their transfection abilities, either alone or with the co-lipid DOPE, were evaluated in HEK293-T7 cells. We found that imidazolium lipophosphoramidate 7 a/DOPE lipoplexes gave the most efficient transfection with low toxicity (15 %). The luciferase activity was 100 times higher than that obtained with DOTAP/DOPE lipoplexes. The size, zeta potential, pDNA-liposome interactions and cellular uptakes of the lipoplexes were determined. No definitive correlation between the zeta potential values and the transfection efficiencies could be established, but the uptake of lipoplexes by the cells was correlated with their final transfection efficiencies. Our results show that imidazolium phosphoramidate lipids constitute a potential new class of cationic lipids for gene transfer.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Synthesis and Transfection Activity of New Cationic Phosphoramidate Lipids: High Efficiency of an Imidazolium Derivative

Mével¹,

Breuzard²,

Yaouanc³

et al. 2008

ChemBioChem

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“…Our own experiments with the phosphonolipids family, showed that the substitution of an ammonium with a phosphonium or an arsonium polar head results in increased efficacy (up to seven times depending on the cell model used) and reduced toxicity. As an example, the lipophosphoramidate, KLN47, with an arsonium polar head group and two oleic chains gave higher transfection results in mice lungs after intravenous injection (IV) than the homologous ammonium compound GL73 [22,23]. Modifications effecting the nature of the fatty chains were also performed.…”

Section: The Development Of Monocationic Lipids For Use In Gene Delivmentioning

confidence: 99%

Synthetic vectors for gene delivery: An overview of their evolution depending on routes of administration.

Belmadi

Midoux

Loyer

et al. 2015

Biotechnology Journal

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Nucleic acid delivery constitutes an emerging therapeutic strategy to cure various human pathologies. This therapy consists of introducing genetic material into the whole body or isolated cells to correct a cellular abnormality or disfunction. As with any drug, the main objective of nucleic acid delivery is to establish optimal balance between efficacy and tolerance. The methods of administration and the vectors used are selected depending on whether the goal of treatment is the production of an active protein; the replacement of a missing or inactive gene; or the combat of acquired diseases, such as cancer or AIDS. In that sense, synthetic vectors represent a valuable solution because they are well characterized, their structure can be fine tuned, and their potential toxicity can be reduced, since toxicity depends on the composition of the formulations. Here we review various synthetic vectors for gene delivery and address the question of their biodistribution as a function of the route of administration. We highlight the modifications to vectors structure and formulations necessary to overcome the major hurdles limiting the effectiveness of nucleic acid therapies.

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“…Several structural modifications were performed including variations of the hydrophobic chain length (Le Bolc'h et al 1995;Floch et al 1998), the structure of the linker and of the polar head group Mevel et al 2007). An interesting structural modification was the substitution of the trimethylammonium polar head group by either a trimethylphosphonium or a trimethylarsonium, to decrease the toxicity of the cationic lipids Guenin et al 2000;Picquet et al 2005). The rationale for this was based on a previous study that had used a similar strategy (Stekar et al 1995) and on the fact that trimethylarsonium groups have been found in natural phospholipids (arsenocholine) from marine organisms (Junk et al 1990).…”

Section: Natural Lipid From Plasma Membranementioning

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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Cationic Lipophosphoramidates and Lipophosphoguanidines Are Very Efficient for in Vivo DNA Delivery

Cited by 60 publications

References 13 publications

Synthesis and Transfection Activity of New Cationic Phosphoramidate Lipids: High Efficiency of an Imidazolium Derivative

Synthesis and Transfection Activity of New Cationic Phosphoramidate Lipids: High Efficiency of an Imidazolium Derivative

Synthetic vectors for gene delivery: An overview of their evolution depending on routes of administration.

Nature as a source of inspiration for cationic lipid synthesis

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