But in many cases the expression has been transient or limited. And in genetic disorders ongoing expression is needed. Gruenert and his colleagues have developed an approach for introducing gene sequence that is intended to avoid the potential problem of cell-inappropriate gene expression. The hope is that the cell's own control machinery will recognize small fragments of homologous DNA and, with this recognition, initiate enzymatic genetic engineering by removing the mutated gene and splicing the new, therapeutic DNA into place. The homologous segment targets the mutated portion of the gene by some as yet unknown enzymatic mechanism.
Preliminary studies indicate some success.
Cell culture evidence suggests that only six percent of the lung epithelial cells needs to be altered to change the ion transport characteristics to approach that of normal, says Gruenert. Another alternative form of gene therapy reported at the Paris symposium takes the opposite approach to genetic reengineering. In this case, parts of chromosomes, as opposed to mere fragments of DNA, are injected into cells. But the goal here is, again, to provide the cell's regulatory machinery with the genetic information that pertains to the mutated gene of interest. The technique, says Gruenert, could be particularly appropriate for such diseases as Duchennes muscular dystrophy.