Methods and devices for delivering aerosolized formulations containing
polynucleotides to specified regions within a subject's respiratory tract
are disclosed. The methods find use in the delivery of ribozymes,
antisense polynucleotides, and DNA and RNA expression vectors into airway
epithelial cells, alveoli, pulmonary macrophages and other cells in the
respiratory tract (including the oropharynx, nose, nasopharynx). These
methods may be used for optimization of transfection efficiency and
expression in vivo, and for in vivo expression, for example for
generating an immune response, or inducing immunological tolerance.