Direct gene transfer into the rat pancreas using DNA-liposomes.
BACKGROUND
Pancreatic cancer represents a malignancy with very poor clinical prognosis and limited therapeutic potential. Recent developments of gene transfer technology offer new therapeutic avenues by delivering recombinant genes directly into normal or neoplastic tissue in vivo.


METHODS
Here we show that the LacZ marker gene, complexed to cationic liposomes, can be introduced into the pancreas by either intraductal or intra-arterial injection. Expression of the beta-galactosidase gene product was monitored by polymerase chain reaction and histochemistry.


RESULTS
Up to 28 days after in vivo gene transfer, beta-galactosidase activity could be demonstrated in the pancreas. Intraductal application induced gene expression in lining duct cells preferentially. Twenty-four hours after intraductal injection of liposomes, a dose-dependent, transient increase in serum amylase levels was detected. Nevertheless, no histological signs of pancreatitis were evident. Intra-arterial injection resulted in beta-galactosidase expression in endothelial cells of intrapancreatic arteries, as well as in the spleen, lymph nodes and liver, but not in ductal cells of the pancreas. Only occasionally were acinar cells positive for blue staining by either type of treatment.


CONCLUSIONS
These experiments demonstrate that in vivo gene transfer into the pancreas is feasible using DNA-liposome complexes. Furthermore, the route of administration largely determines cell type specificity and side-effects. This technique might have an impact for the development of gene therapy strategies for pancreatic diseases.
Schmid
R M
RM
Department of Internal Medicine, Ulm University, Germany.
Weidenbach
H
H
Yamagushi
H
H
Lührs
H
H
Liptay
S
S
Adler
G
G
D000681:Amylases / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004274:DNA, Recombinant / Q000008:administration & dosage* / Q000235:genetics*; D015870:Gene Expression; D018014:Gene Transfer Techniques; D005819:Genetic Markers; D015316:Genetic Therapy / Q000379:methods; D007763:Lac Operon; D008081:Liposomes; D010179:Pancreas / Q000201:enzymology; D010190:Pancreatic Neoplasms / Q000628:therapy; D016133:Polymerase Chain Reaction; D051381:Rats; D017208:Rats, Wistar; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D017931:DNA Primers; D004274:DNA, Recombinant; D005819:Genetic Markers; D008081:Liposomes; D000681:Amylases; D001616:beta-Galactosidase