ABSTRACT
Many inherited and acquired pulmonary disorders without satisfactory therapies may be amenable to gene therapy. Despite numerous advances, efficient delivery and expression of the therapeutic transgene at physiological levels for phenotypic correction of disease has proved elusive. This article focuses on various strategies aimed at achieving targeted delivery to the lungs. Both physical methods and biological targeting have been successfully applied in various gene delivery systems. Targeting of different cell types has been achieved by pseudotyping of viral vectors with capsids from different serotypes and modification of nonviral vectors with targeting ligands. Both classes of vectors are discussed with respect to their gene delivery and expression efficiencies, longevity of expression and immunogenicity. Moreover, gene therapy clinical trials for different lung diseases are discussed.
Subject(s)
Gene Transfer Techniques , Genetic Therapy/methods , Lung Diseases/therapy , Lung/metabolism , Animals , Biological Transport , Genetic Vectors , Humans , Lung Diseases/genetics , Lung Diseases/metabolismABSTRACT
Gene therapy holds promise for the treatment of a range of inherited pulmonary disorders. However, efficient delivery and expression of the therapeutic transgene at levels sufficient to result in phenotypic correction of the diseased state has proved elusive. This review focuses on the development of gene delivery strategies for the lungs. One of the principal prerequisites for successful gene therapy is the delivery of gene vectors to the target area within a tissue and to target cells within that area. Physical and biological targeting of the gene vectors and its application in various models is discussed. Subsequently, both viral and non-viral vectors are addressed with respect to their transfection efficiency in different lung cells, the longevity of expression and their immunogenicity. Also, the various methods for pulmonary gene delivery are evaluated for their merits and limitations.
