Molecular basis of alpha 1-antitrypsin deficiency and its potential therapy by gene transfer.

The gene for alpha 1-antitrypsin, a serum anti-protease, has been cloned and sequenced. The underlying mutation in the PiZ allele has been identified as a G to A conversion giving rise to the substitution of glu by lys at position 342. Preparation of specific probes has allowed prenatal diagnosis. Recombinant retroviruses containing the normal human alpha 1-antitrypsin gene have been constructed and used to infect NIH3T3 cells. Analysis of DNA, RNA and protein indicate that successful incorporation of the alpha 1-antitrypsin was achieved and that the gene was capable of being expressed. The feasibility of genetic replacement therapy has been demonstrated and further experiments justified.