Formation of LID vector complexes in water alters physicochemical properties and enhances pulmonary gene expression in vivo

Gene Therapy
R Gisli JenkinsStephen L Hart

Abstract

There is currently an urgent need to develop efficient gene-delivery systems for the lung that are free of inflammatory effects. The LID vector is a synthetic gene delivery system, comprised of lipofectin (L), an integrin-targeting peptide (I) and DNA (D) that has previously been shown to have high transfection efficiency in the lung. We have assessed the effect of alternative methods of complex preparation on structural features of the complex, levels and duration of reporter gene expression and the host response to the LID vector. We have demonstrated that making the complex in water affects the structure of the LID complexes making them smaller and more stable with a more cationic surface charge than complexes prepared in phosphate-buffered saline (PBS). When the LID vector was constituted in water and instilled intratracheally into the lungs of mice there was a 10-fold increase in luciferase activity compared with preparation in PBS. Furthermore, luciferase activity was still evident 1 week following vector instillation. This enhancement may be because of altered complex structure, although effects of the hypotonic vector solution on the lung cannot be excluded. The inflammatory effects of instilling the LID vector in water...Continue Reading

References

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Citations

Feb 4, 2010·Cell Biology and Toxicology·Stephen L Hart
Apr 5, 2008·Molecular Therapy : the Journal of the American Society of Gene Therapy·Aristides D TagalakisStephen L Hart
Jun 24, 2009·Expert Opinion on Biological Therapy·I A PringleD R Gill
Jun 1, 2011·Biomaterials·Aristides D TagalakisStephen L Hart
Jun 19, 2016·Journal of Controlled Release : Official Journal of the Controlled Release Society·Mehdi RezaeeBizhan Malaekeh-Nikouei
Oct 9, 2003·The Journal of Gene Medicine·Robert E WhiteMichael R James
May 22, 2008·Molecular BioSystems·John B WongHelen C Hailes
Jul 5, 2008·Organic & Biomolecular Chemistry·Christopher A HurleyHelen C Hailes
Mar 6, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Stephanie M GrosseStephen L Hart
Jan 20, 2005·The Biochemical Journal·Tim W R LeeG Eric Blair
Jan 31, 2004·The Journal of Organic Chemistry·Christopher A HurleyAlethea B Tabor

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