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 s...

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Bibliographic Details
Published in:European journal of clinical investigation 1998-03, Vol.28 (3), p.220-226
Main Authors: SCHMID, R. M, WEIDENBACH, H, YAMAGUSHI, H, LÜHRS, H, LIPTAY, S, ADLER, G
Format: Article
Language:English
Subjects:
Amylases - metabolism
Animals
Base Sequence
beta-Galactosidase - genetics
beta-Galactosidase - metabolism
Biological and medical sciences
Biotechnology
DNA Primers - genetics
DNA, Recombinant - administration & dosage
DNA, Recombinant - genetics
Fundamental and applied biological sciences. Psychology
Gene Expression
Gene therapy
gene transfer
Gene Transfer Techniques
Genetic Markers
Genetic Therapy - methods
Health. Pharmaceutical industry
in vivo
Industrial applications and implications. Economical aspects
Lac Operon
LacZ
Liposomes
pancreas
Pancreas - enzymology
Pancreatic Neoplasms - therapy
Polymerase Chain Reaction
Rats
Rats, Wistar
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Summary: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 β‐galactosidase gene product was monitored by polymerase chain reaction and histochemistry. Results Up to 28 days after in vivo gene transfer, β‐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 β‐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. Conclusion 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.
ISSN:0014-2972
1365-2362
DOI:10.1046/j.1365-2362.1998.00269.x