Size, diffusibility and transfection performance of linear PEI/DNA complexes in the mouse central nervous system.
Gene Ther
; 5(5): 712-7, 1998 May.
Article
in En
| MEDLINE
| ID: mdl-9797878
ABSTRACT
Currently in vivo gene delivery by synthetic vectors is hindered by the limited diffusibility of complexes in extra-cellular fluids and matrices. Here we show that certain formulations of plasmid DNA with linear polyethylenimine (22 kDa PEI, ExGene 500) can produce complexes that are sufficiently small and stable in physiological fluids so as to provide high diffusibility. When plasmid DNA was formulated with 22 kDa PEI in 5% glucose, it produced a homogeneous population of complexes with mean diameters ranging from 30 to 100 nm according to the amount of PEI used. In contrast, formulation in physiological saline produced complexes an order of magnitude greater (> or = 1 micron). Intraventricular injection of complexes formulated in glu-cose showed the complexes to be highly diffusible in the cerebrospinal fluid of newborn and adult mice, diffusing from a single site of injection throughout the entire brain ventricular spaces. Transfection efficiency was followed by histochemistry of beta-galactosidase activity and double immunocytochemistry was used to identify the cells transfected. Transgene expression was found in both neurons and glia adjacent to ventricular spaces. Thus, this method of formulation is promising for in vivo work and may well be adaptable to other vectors and physiological models.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Polyethyleneimine
/
Brain
/
DNA, Circular
/
Transfection
/
Gene Transfer Techniques
/
Genetic Vectors
Limits:
Animals
Language:
En
Journal:
Gene Ther
Journal subject:
GENETICA MEDICA
/
TERAPEUTICA
Year:
1998
Document type:
Article
Affiliation country:
France