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- Article] Self-assembled lamellar complexes of siRNA with lipidic aminoglycoside derivatives promote efficient siRNA delivery and interference
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DocNo of ILP: 4097
Doc. Type: Article
Title: Self-assembled lamellar complexes of siRNA with lipidic aminoglycoside derivatives promote efficient siRNA delivery and interference
Authors: Desigaux, L; Sainlos, M; Lambert, O; Chevre, R; Letrou-Bonneval, E; Vigneron, JP; Lehn, P; Lehn, JM; Pitard, B
Full Name of Authors: Desigaux, Lea; Sainlos, Matthieu; Lambert, Olivier; Chevre, Raphael; Letrou-Bonneval, Emilie; Vigneron, Jean-Pierre; Lehn, Pierre; Lehn, Jean-Marie; Pitard, Bruno
Keywords by Author: gene silencing; gene transfer vectors; transfection
Keywords Plus: RNA INTERFERENCE; GENE-TRANSFER; CATIONIC LIPIDS; IN-VIVO; SUPRAMOLECULAR ASSEMBLIES; LIPOSOME COMPLEXES; MAMMALIAN-CELLS; PLASMID DNA; TRANSFECTION; LIPOPLEXES
Abstract: RNA interference requires efficient delivery of small doublestranded RNA molecules into the target cells and their subsequent incorporation into RNA-induced silencing complexes. Although current cationic lipids commonly used for DNA transfection have also been used for siRNA transfection, a clear need still exists for better siRNA delivery to improve the gene silencing efficiency. We synthesized a series of cationic lipids characterized by head groups bearing various aminoglycosides for specific interaction with RNA. siRNA complexation with such lipidic aminoglycoside derivatives exhibited three lipid/siRNA ratio-dependent domains of colloidal stability. Fluorescence and dynamic light-scattering experiments showed that cationic lipid/siRNA complexes were formed at lower charge ratios, exhibited a reduced zone of colloidal instability, and had smaller mean diameters compared with our previously described guaniclinium-based cationic lipids. Cryo-transmission electron microscopy and x-ray-scattering experiments showed that, although the final in toto morphology of the lipid/siRNA complexes depended on the aminoglycoside type, there was a general supramolecular arrangement consisting of ordered lamellar domains with an even spacing of 67 A. The most active cationic lipid/siRNA complexes for gene silencing were obtained with 4,5-disubstituted 2-deoxystreptamine aminoglycoside derivatives and were characterized by the siRNA being entrapped in small particles exhibiting lamellar microdomains corresponding to siRNA molecules sandwiched between the lipid bilayers. These results clearly show that lipiclic aminoglycoside derivatives constitute a versatile class of siRNA nanocarriers allowing efficient gene silencing.
Cate of OECD: Other natural sciences
Year of Publication: 2007
Business Area: other
Detail Business: medicine & science
Country: USA
Study Area:
Name of Journal: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Language: English
Country of Authors: Inst Natl Sante & Rech Med, U533, F-44035 Nantes, France; Coll France, Lab Chim Interact Mol, F-75005 Paris, France; Univ Nantes, Fac Med, Inst Thorax, F-44035 Nantes, France; Univ Bordeaux 1, Unite Mixte Rech 5248, CNRS, F-33405 Talence, France; Univ Bretagne Occidentale, Ctr Hosp Univ Brest, F-29200 Brest, France; In Cell Art, F-44093 Nantes, France
Press Adress: Lehn, JM (reprint author), Inst Natl Sante & Rech Med, U533, F-44035 Nantes, France.
Email Address: lehn@isis.u-strasbg.fr; bruno.pitard@incellart.com
Citaion:
Funding:
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Number of Citaion: 28
Publication: NATL ACAD SCIENCES
City of Publication: WASHINGTON
Address of Publication: 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
ISSN: 0027-8424
29-Character Source Abbreviation: P NATL ACAD SCI USA
ISO Source Abbreviation: Proc. Natl. Acad. Sci. U. S. A.
Volume: 104
Version: 42
Start of File: 16534
End of File: 16539
DOI: 10.1073/pnas.0707431104
Number of Pages: 6
Web of Science Category: Multidisciplinary Sciences
Subject Category: Science & Technology - Other Topics
Document Delivery Number: 223MA
Unique Article Identifier: WOS:000250373400028
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