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Systemic circulation of poly(l-lysine)/DNA vectors is
influenced by polycation molecular weight and type of
DNA: differential circulation in mice and rats and the
implications for human gene therapy
by Christopher M. Ward, Martin L. Read, and Leonard W. Seymour
Blood
Volume 97(8):2221-2229
April 15, 2001
©2001 by American Society of Hematology
pLL211/DNA complexes exhibit increased circulation in mice compared to pLL20/DNA
complexes and are unaffected by the type of DNA used.pLL/DNA complexes, formed with pLL20
(20 kd pLL/DNA) or pLL211 (211 kd pLL/DNA), and either DNAct(▪), DNAcp (■), or DNAlp (...
Christopher M. Ward et al. Blood 2001;97:2221-2229
©2001 by American Society of Hematology
pLL20/DNA complexes display increased aggregation in salt compared to
pLL211/DNA.pLL/DNAcp complexes were analyzed for light scattering on a Zetasizer photon
correlation spectroscope in the presence or absence of 150 mM NaCl. pLL20/DNAcp (●, +NaCl; ♦,
−NaCl...
Christopher M. Ward et al. Blood 2001;97:2221-2229
©2001 by American Society of Hematology
pLL20/DNA complexes, but not pLL211/DNA, show punctate distribution of radioactivity in blood
smears, and both types of complexes bind erythrocytes.pLL20/DNAct or pLL211/DNAct
complexes were administered intravenously to female Balb/c mice (0.1 mL of 10 μg/...
Christopher M. Ward et al. Blood 2001;97:2221-2229
©2001 by American Society of Hematology
pLL20/DNA and pLL211/DNA complexes associate with Kupffer cells in mice.pLL20/DNAct or
pLL211/DNAct complexes were administered intravenously to female Balb/c mice (0.1 mL of 10
μg/mL DNA).
Christopher M. Ward et al. Blood 2001;97:2221-2229
©2001 by American Society of Hematology
pLL20/DNAct complexes, but not pLL211/DNA, fix mouse complement C3 independently of
immunoglobulins.Biotin-pLL20/DNAct or biotin-pLL211/DNAct complexes were immobilized on
streptavidin magnetic beads and incubated in mouse serum at 37°C for 5 minutes.
Christopher M. Ward et al. Blood 2001;97:2221-2229
©2001 by American Society of Hematology
pLL20/DNA complexes lead to increased levels of CR3-expressing cells within the liver of
mice.Method as for Figure 4.
Christopher M. Ward et al. Blood 2001;97:2221-2229
©2001 by American Society of Hematology
pLL20/DNAct and pLL211/DNAct complexes are rapidly removed from the circulation of female
Wistar rats but do not bind complement C3 in vitro.(A) pLL20/DNAct (♦) or pLL211/DNAct (▪)
complexes were administered intravenously to female Wistar rats (1.0 mL of 1...
Christopher M. Ward et al. Blood 2001;97:2221-2229
©2001 by American Society of Hematology
pLL20/DNAct and pLL211/DNAct complexes fix human complement C3 and bind IgG but are not
hematotoxic in vitro.(A) Hematotoxicity of pLL20/DNAct (■) or pLL211/DNAct (▪) complexes was
determined by their incubation in human or rat blood at 37°C for 1 hour.
Christopher M. Ward et al. Blood 2001;97:2221-2229
©2001 by American Society of Hematology