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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
pharmacology, toxicology and pharmaceutics
DODAG; a versatile new cationic lipid that mediates efficient delivery of pDNA and siRNA
Journal of Controlled Release, Volume 143, No. 2, Year 2010
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Description
We report the syntheses of novel cationic lipids comprised of cholesteryl-moieties linked to guanidinium functional groups, and also cationic lipids comprising a dialkylglycylamide moiety conjugated with a polyamine or a guanidinium functional group. In plasmid DNA (pDNA) transfection studies, these cationic lipids were formulated into cationic liposomes with the neutral co-lipid dioleoyl-L-α-phosphatidylethanolamine (DOPE) or with a recently reported neutral lipophosphoramidate derivative of histamine (MM27). We observe that cationic liposomes prepared from the cationic lipid N′. ,N′-dioctadecyl. -N-4,8-diaza-10-aminodecanoylglycine amide (DODAG) and DOPE frequently mediate the highest levels of transfection in vitro in all three different cell lines studied (OVCAR-3, IGROV-1 and HeLa) both in the presence or absence of serum. In addition, in vitro cellular toxicity was found to be minimal. Alternatively, we observe that DODAG alone forms lipoplex nanoparticles with small interfering RNA (siRNA) that are able to mediate the functional delivery of two previously validated anti-hepatitis B virus (HBV) - siRNAs to murine liver in vivo with minimal observable liver toxicity and immune stimulation. Specific knock-down of HBV infection parameters (virion and hepatic mRNA levels) is observed that is at least equivalent to the impact of extensive treatment with lamivudine (a licensed antiviral drug). © 2009 Elsevier B.V.
Authors & Co-Authors
Mével, Mathieu
United Kingdom, London
Imperial College London
Kamaly, Nazila
United Kingdom, London
Imperial College London
Carmona, Sergio C.
South Africa, Johannesburg
School of Clinical Medicine
Oliver, Morag H.
United Kingdom, London
Imperial College London
Jorgensen, Michael R.
United Kingdom, London
Imperial College London
Crowther, Carol
South Africa, Johannesburg
School of Clinical Medicine
Salazar, Felix H.
United States, Palo Alto
Stanford University
United States
Hepadnavirus Testing, Inc. Mountain View
Marion, Patricia L.
United States
Hepadnavirus Testing, Inc. Mountain View
Fujino, Masato
Japan, Tokyo
Rnai Company Ltd.
Natori, Yukikazu
Japan, Tokyo
Rnai Company Ltd.
Thanou, Maya M.
United Kingdom, London
Imperial College London
Arbuthnot, Patrick B.
South Africa, Johannesburg
School of Clinical Medicine
Yaouanc, Jean Jacques
France, Brest
Faculté Des Sciences et Techniques - Université de Brest Ubo
Jaffrès, Paul Alain
France, Brest
Faculté Des Sciences et Techniques - Université de Brest Ubo
Miller, Andrew D.
United Kingdom, London
Imperial College London
United Kingdom, London
Imuthes Ltd.
Statistics
Citations: 103
Authors: 15
Affiliations: 7
Identifiers
Doi:
10.1016/j.jconrel.2009.12.001
ISSN:
01683659
Research Areas
Genetics And Genomics
Infectious Diseases