Av. Kabanov et Va. Kabanov, INTERPOLYELECTROLYTE COMPLEXES OF NUCLEIC -ACIDS AS A MEANS FOR TARGETED DELIVERY OF GENETIC MATERIAL TO THE CELL, Vysokomolekularnye soedinenia. Seria A, 36(2), 1994, pp. 198-211
The prospects of using interpolyelectrolyte complexes (IPEC) of DNA wi
th polycations to deliver genetic material to the cell are reviewed. I
PEC are formed in solutions of DNA and polycation due to a cooperative
system of interchain electrostatic bonds. Physicochemical characteris
tics of IPEC, including solubility and the size and the surface charge
of IPEC particles are controlled by IPEC composition, which is descri
bed as the polycation: DNA ratio expressed in base-mole units of each
component. Incorporation into IPEC significantly affects the propertie
s of DNA; it becomes more compact and stable to cleavage by nucleases.
Transformation of B. subtilis is used to illustrate the incorporation
of plasmid into IPEC with carbochain polycation, which significantly
enhances the transforming activity. These IPEC can bind to animal cell
s and exhibit endocytosis. An effective procedure for transfection of
animal cells is reported, which involves incorporation of plasmid DNA
into complexes with carbochain polycations and lipopolyamines. IPEC-ba
sed structures are also used to deliver DNA via a receptor-mediated pa
thway. For this purpose, the molecule of polycation [poly(L-lysine)] t
hat enters into the complex is covalently bound to the ligand; this en
sures endocytosis of IPEC and transfection of the cells. A similar app
roach was used for targeted delivery of genetic material to the target
cells in the body. In this case, the polycation combines with antibod
ies or other molecules that can selectively interact with the target.