Effect of multiple gene transfers of insulinlike growth factor I complementary DNA gene constructs in rats after thermal injury.
OBJECTIVE
Multiple subcutaneous injections of cholesterol-containing cationic liposomes encapsulating the complementary DNA (cDNA) gene for insulinlike growth factor I (IGF-I) increase the rate of transfected skin cells and result in increased IGF-I protein levels in the skin with subsequent improvement in wound healing when compared with a single injection.


METHODS
Laboratory.


METHODS
Twenty-four adult male Sprague-Dawley rats (350-375 g) received a full-thickness scald burn on 60% of their body surface. These rats were randomly divided to receive either 1 injection of liposomes containing 2.2 microg-cytomegalovirus-driven cDNA coding for IGF-I and 0.2 microg of the Lac Z gene cDNA construct, or 2 injections of liposomes containing 2.2 microg cytomegalovirus-driven cDNA coding for IGF-I and 0.2 microg of the Lac Z gene cDNA construct.


METHODS
Transfection rates and IGF-I protein levels in the skin and physiological responses to the IGF-I gene therapy, evaluated from changes in body weight, protein content in serum and liver, and the rate of burn wound healing.


RESULTS
There was a significant decrease in transfection rate and IGF-I protein expression distal from the injection site in animals receiving 1 injection, as compared with a consistent increase in rats receiving multiple injections. Multiple injections improved the response to thermal trauma by increasing the extent of the healed burn wound 33 days after thermal injury (single injection, 31% +/- 1% vs multiple injections, 38% +/- 2%), total serum protein (single injection, 52 +/- 0.5 g/L vs multiple injections, 55 +/- 0.6 g/L), and total liver protein (single injection, 82.0 +/- 0.3 mg/mL vs multiple injections, 91.0 +/- 3.8 mg/mL), P<.05.


CONCLUSIONS
Gene transfer rates can be increased by multiple injections of liposomes encapsulating IGF-I cDNA constructs. Increased transfer results in greater IGF-I protein skin concentrations, accelerated wound healing, and increased serum and liver protein concentrations. The clinical relevance of these findings is that liposomal gene constructs should be applied in well-defined distances to improve gene transfer in the skin, and thus clinical outcome after thermal injury.
Jeschke
M G
MG
Shriners Hospital for Children, Galveston, Tex 77550, USA.
Barrow
R E
RE
Hawkins
H K
HK
Chrysopoulo
M T
MT
Perez-Polo
J R
JR
Herndon
D N
DN
D000818:Animals; D002056:Burns / Q000628:therapy*; D018076:DNA, Complementary / Q000008:administration & dosage*; D004337:Drug Carriers; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008081:Liposomes; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D018076:DNA, Complementary; D004337:Drug Carriers; D008081:Liposomes; D007334:Insulin-Like Growth Factor I