Pulmonary gene therapy

Inoshima I, Kuwano K, Hamada N, et al. Anti-monocyte chemoattractant protein-1 gene therapy attenuates pulmonary fibrosis in mice. Am J Physiol Lung Cell Mol Physiol 2004 286(5) L1038-L1044. 

Reynolds, A.M., Xia, W., Holmes, M.D., Hodge, S.J., Danilov, S., Curiel, D.T., Morrell, N.W., and Reynolds, P.N. (2007) Bone morphogenetic protein type 2 receptor gene therapy attenuates hypoxic pulmonary hypertension. Am. J. Physiol. Lung Cell Mol. Physiol. 292, L1182-L1192. 

Densmore CL (2006) Advances in noninvasive pulmonary gene therapy. Curr Drug Deliv 3( 1 ) 55—63. 

The major expansion in this present volume concerns the subjects of proteomics and gene therapy, both of which offer so much promise for the future. Pulmonary administration is another likely route of delivery for the future and this is reviewed separately. Conventional wisdom suggests that proteins cannot be delivered orally but there is strong evidence suggesting that this is not always true and this is another exciting area that is reviewed here. The earlier review of vaccines has been expanded considerably since this is another area of current interest with potential for wider future application. 

Kolb M, Martin G, Medina M, Ask K, et al. 2006. Gene therapy for pulmonary diseases. Chest. 130 879-884. 

Liu L, Liu H, Visner G, Fletcher BS. 2006. Sleeping beauty-mediated eNOS gene therapy attenuates monocrotaline-induced pulmonary hypertension in rats. FASEB J. 20 2594-2596. 

Gautam, A., Densmore, C.L. and Waldrep, J.C. (2001) Pulmonary cytokine responses associated with PEI-DNA aerosol gene therapy. Gene Ther., 8,254-257. 

T. Shirakawa, S. C. Ko, T. A. Gardner, J. Cheon, T. Miyamoto, A. Gotoh, L. W. Chung, and C. Kao, In vivo suppression of osteosarcoma pulmonary metastasis with intravenous osteocalcin promoter-based toxic gene therapy, Cancer Gene Ther. 5 274 (1998). 

Theoretically, a number of other diseases affecting the pulmonary interstitium might be treated with gene therapy. These include interstitial pneumonitides and idiopathic pulmonary fibrosis. These approaches will depend upon further advancements in the study of the basic pathobiology of these disorders. 

Rolls, J. K., Lei, D., Nelson, S., Summer, W. R. and Shellito, J. E. (1997). Pulmonary cytokine gene therapy. Adenoviral-mediated murine interferon gene transfer compartmentally activates alveolar macrophages and enhances bacterial clearance. Chest 111, 104S. 

Rolls, J. R., Ye, P. and Shellito, J. E. (2001). Gene therapy to modify pulmonary host defenses. Semin. Respir. Infect. 16, 18-26. 

New technologies are also addressing the pulmonary delivery of the new biotherapeutics , i.e. the products of biotechnology and molecular biology such as peptides, proteins and gene therapies which have been described in detail in Chapter 1 (Section 1.6). Biopharmaceuticals under investigation for potential pulmonary delivery include those for local, and systemic, effects (Table 10.4). 

Pulmonary gene therapy is attractive for the treatmment of chronic bronchitis, cystic fibrosis, a-1 antitrypsin deficiency, familial emphysema, asthma, pulmonary infections, surfactant deficiency, pulmonary hypertension, lung cancer, and malignant mesothelioma. The pulmonary endothelium may act as a bioreactor for the production and secretion of therapeutic proteins, such as clotting factors and erythropoietin into the blood circulation. There is a potential benefit for acquired lung diseases, as well as cancers, to be controlled and possibly treated by expression of cytokines, surfactant, antioxidant enzymes, or mucoproteins within lung cells. 

Pulmonary delivery of liposomes has focused on the treatment of asthma, infectious diseases, genetic diseases (cystic fibrosis), and lung injury and lately on gene therapy. 

Li H-Y, Neill H, Innocent R, Seville P, William.son I. Birchatl iC. Enhanced dispersibility and deposition of spray-dried powders for pulmonary gene therapy, i Drug Target 2003 II 425-32. 

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