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Article Dans Une Revue Biochemistry Année : 2007

Biophysical characterization of an integrin-targeted lipopolyplex gene delivery vector

M. F. Mohd Mustapa
  • Fonction : Auteur
P. C. Bell
  • Fonction : Auteur
C. A. Hurley
  • Fonction : Auteur
A. Nicol
  • Fonction : Auteur
S. Sarkar
  • Fonction : Auteur
M. J. Writer
  • Fonction : Auteur
S. E. Barker
  • Fonction : Auteur
J. B. Wong
  • Fonction : Auteur
M. A. Pilkington-Miksa
  • Fonction : Auteur
B. Papahadjopoulos-Sternberg
  • Fonction : Auteur
P. A. Shamlou
  • Fonction : Auteur
H. C. Hailes
  • Fonction : Auteur
S. L. Hart
  • Fonction : Auteur
D. Zicha
  • Fonction : Auteur
A. B. Tabor
  • Fonction : Auteur

Résumé

Nonviral gene delivery vectors now show good therapeutic potential: however, detailed characterization of the composition and macromolecular organization of such particles remains a challenge. This paper describes experiments to elucidate the structure of a ternary, targeted, lipopolyplex synthetic vector, the LID complex. This consists of a lipid component, Lipofectin (L) (1: 1 DOTMA:DOPE), plasmid DNA (D), and a dual-function, cationic peptide component (1) containing DNA condensation and integrintargeting sequences. Fluorophore-labeled lipid, peptide, and DNA components were used to formulate the vector, and the stoichiometry of the particles was established by fluorescence correlation spectroscopy (FCS). The size of the complex was measured by FCS, and the sizes of LID, L, LD, and ID complexes were measured by dynamic light scattering (DLS). Fluorescence quenching experiments and freezefracture electron microscopy were then used to demonstrate the arrangement of the lipid, peptide, and DNA components within the complex. These experiments showed that the cationic portion of the peptide, 1, interacts with the plasmid DNA, resulting in a tightly condensed DNA-peptide inner core; this is surrounded by a disordered lipid layer, from which the integrin-targeting sequence of the peptide partially protrudes.

Dates et versions

hal-00463306 , version 1 (11-03-2010)

Identifiants

Citer

M. F. Mohd Mustapa, P. C. Bell, C. A. Hurley, A. Nicol, E. Guenin, et al.. Biophysical characterization of an integrin-targeted lipopolyplex gene delivery vector. Biochemistry, 2007, 46 (45), pp.12930-12944. ⟨10.1021/bi701014y⟩. ⟨hal-00463306⟩
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