Document Detail


Isolated lung liposome-mediated gene transfer produces organ-specific transgenic expression.
MedLine Citation:
PMID:  9768949     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Gene therapy is a promising strategy for the treatment of inoperable pulmonary tumors and rejection after lung transplantation. However, unlike ex vivo administration, intravenous in vivo transfection lacks organ specificity and has a limited duration of expression. The objectives of this study were to limit transfection to a single lung and to increase the duration of gene expression in vivo. METHODS: Sixteen male Fisher rats were anesthetized and divided into two groups. Animals in group I (n = 7) received an intrajugular administration of 1,320 microg of chloramphenicol acetyl transferase (CAT) complementary DNA complexed with cationic liposomes. Animals in group II (n = 9) received 660 microg of CAT complementary DNA complexed with cationic liposomes into the pulmonary artery of an isolated left lung over 10 minutes. After 40 minutes of incubation, the lung was flushed with 10 mL of normal saline solution, and the perfusate was suctioned through a left pulmonary venotomy. The circulation to the left lung was then restored. After 48 hours, the animals were divided into subgroups (a and b) and CAT activity was assessed in the lungs, hearts, livers, and kidneys of groups Ia (n = 3) and IIa (n = 5). After 21 days, CAT activity was assessed in the left lungs of groups Ib (n = 4) and IIb (n = 4). RESULTS: After 48 hours, animals that had received intravenous administration of CAT cDNA showed strong expression in the lungs and hearts and negligible expression in the livers and kidneys. In contrast, animals in group IIa, which had received isolated left lung perfusion of CAT cDNA showed expression only in the left lung. After 21 days, the left lungs of animals in group Ib, which had received intravenous administration of CAT complementary DNA, showed no CAT expression, but the left lungs of animals in group IIb, which had received isolated left lung perfusion of CAT complementary DNA, exhibited strong CAT expression. CONCLUSIONS: Compared with intravenous administration, isolated lung liposome-mediated gene transfer provides prolonged organ-specific gene expression. This provides a useful model to study the effects of gene therapy on pulmonary tumors, which may have further application when gene therapy is used in clinical practice.
Authors:
R Lee; C H Boasquevisque; M M Boglione; M Hiratsuka; R K Scheule; J D Cooper; G A Patterson
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Annals of thoracic surgery     Volume:  66     ISSN:  0003-4975     ISO Abbreviation:  Ann. Thorac. Surg.     Publication Date:  1998 Sep 
Date Detail:
Created Date:  1998-10-21     Completed Date:  1998-10-21     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  15030100R     Medline TA:  Ann Thorac Surg     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  903-7     Citation Subset:  AIM; IM    
Affiliation:
Division of Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Chemotherapy, Cancer, Regional Perfusion*
Chloramphenicol O-Acetyltransferase / metabolism
DNA, Complementary / administration & dosage
Gene Expression*
Gene Therapy / methods
Liposomes
Lung* / metabolism
Male
Rats
Rats, Inbred F344
Transfection / methods*
Grant Support
ID/Acronym/Agency:
1 R01 HL 41281/HL/NHLBI NIH HHS; 5 T32 HL07776/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/DNA, Complementary; 0/Liposomes; EC 2.3.1.28/Chloramphenicol O-Acetyltransferase

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