Individuals with single-gene mutations that decrease levels of the protein alpha-1 antitrypsin are at high risk for emphysema at a young age. Researchers have attempted to correct this defect by gene transfer, but with no success in obtaining sustained in vivo expression.
Now a team of investigators led by Darrell Kotton at Boston University School of Medicine has been able to overcome this hurdle by attaining sustained in vivo expression of normal human alpha-1 antitripsin—and at levels that improved emphysema in mice.
The success was achieved by introducing gene-carrying lentviral vectors into the windpipes of mice. The vectors then transferred the genes they were carrying to alveolar macrophages. The cells continued to express the transferred genes for at least 2 years. When vectors carrying the gene responsible for making human alpha-1 antitrypsin was introduced, sustained alpha-1 antitrypsin expression resulted, and disease was reduced.
The investigators suggest that this might provide a therapeutic approach for overcoming lung diseases caused by single-gene defects, such as emphysema resulting from alpha-1 antitrypsin deficiency.