Methods of gene therapy, particular ribozyme-mediated gene replacement methods, are disclosed. Method of treating patients suffering from a disease associated with expression of an abnormal form of a gene, such as alpha-1 antitrypsin mutations, are disclosed. The methods comprise the steps of administering to such a patient a nucleic acid construct encoding a ribozyme and a nucleic acid construct comprising a ribozyme resistant gene encoding a wild type form of the gene product. Recombinant vectors and pharmaceutical compositions for practicing the methods are disclosed.