Abstract: The invention is directed to methods for introducing biologically active peptides into a host by administration of polynucleotides which operatively encode for the peptide of interest. In a preferred embodiment of the invention, a mammal is desensitized to an antigen, in particular an allergen, through administration to the mammal of polynucleotides which operatively encode the antigen. The antigen-encoding polynucleotides are administered to host tissues which have a high concentration of antigen presenting cells in them relative to other host tissues. The method is particularly useful in treating allergies because the allergen-encoding polynucleotides of the invention to induce tolerance while suppressing IgE antibody formation. Devices and compositions for use in the methods of the invention are also described.