Gene therapy.

Abstract

For the past two decades, concerted efforts have been made to treat human disease by replacing nonfunctioning genes in cells or by correcting mutations that produce disease. Successful application of these methods could lead to effective therapies for a variety of genetic and acquired diseases, many of which are not treatable today. Genes can be transferred into cells using either viral vectors, which have evolved the ability to bring their DNA into the host cell, or nonviral vectors, which, until recently, have been much less efficient in their ability to introduce exogenous DNA into cells. Whereas cell transduction is possible in vivo, it is much simpler to accomplish in vitro; for this reason the hematopoietic stem cell has been a favorite target in attempts to implement gene therapy. Stem cells can be partially purified from the blood or marrow, transduced with the gene of interest, and reintroduced into the body. Any genetic disease that responds to transplantation would be expected also to respond to gene therapy. The progress made over the past two decades has resulted in better vectors and ingenious new techniques for correcting mutations in endogenous genes. Although effective gene therapy in humans has continued to be an elusive goal, recent advances lead us to hope that this goal will be realized within the next few years.