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Ann Thorac Surg 1998;66:903-907
© 1998 The Society of Thoracic Surgeons

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Original articles: General Thoracic

Isolated lung liposome-mediated gene transfer produces organ-specific transgenic expression

^a Division of Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, Missouri, USA

Address reprint requests to Dr Patterson, Division of Cardiothoracic Surgery, Washington University School of Medicine, One Barnes Hospital Pl, 3108 Queeny Tower, St. Louis, MO 63110

Presented at the Poster Session of the Thirty-fourth Annual Meeting of The Society of Thoracic Surgeons, New Orleans, LA, Jan 26–28, 1998.

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 µg of chloramphenicol acetyl transferase (CAT) complementary DNA complexed with cationic liposomes. Animals in group II (n = 9) received 660 µg 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.

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