Drawing on his review in the April issue of Nature, he offered two reasons. First, we cannot get genes into a sufficient number of cells in the patient. Second, even if one successfully solves the first problem, the gene usually gets turned off. In general, we are missing an effective delivery system and effective vectors that can give stable, long-term expression. When treating blood or genetic diseases, the hematopoietic stem cell would be the best cell to target.
Expression is complicated because the human body defends itself.
A human cell in vivo can recognize, in ways that are not understood, if the gene is being controlled by normal, authentic human control regions or by viral control regions. When a viral control region is recognized, the human body appears to be able to shut the gene down by methylation or other means. By using authentic human genomic regulatory sequences, Dr. Anderson hopes to bypass this obstacle. However, this too has problems. We know the regulatory sequences for only a few genes, and these sequences are extremely large, most covering tens of kilobases.