<Li> Insertional mutagenesis--If the DNA is integrated in a sensitive spot in the genome, for example in a tumor suppressor gene, the therapy could induce a tumor . This has occurred in clinical trials for X-linked severe combined immunodeficiency (X-SCID) patients, in which hematopoietic stem cells were transduced with a corrective transgene using a retrovirus, and this led to the development of T cell leukemia in 3 of 20 patients . One possible solution is to add a functional tumor suppressor gene to the DNA to be integrated . This may be problematic since the longer the DNA is, the harder it is to integrate into cell genomes . CRISPR technology allows researchers to make much more precise genome changes at exact locations . </Li> <Li> Cost--Alipogene tiparvovec or Glybera, for example, at a cost of $1.6 million per patient, was reported in 2013 to be the world's most expensive drug . </Li> <P> Three patients' deaths have been reported in gene therapy trials, putting the field under close scrutiny . The first was that of Jesse Gelsinger in 1999 . Jesse Gelsinger died because of immune rejection response . One X-SCID patient died of leukemia in 2003 . In 2007, a rheumatoid arthritis patient died from an infection; the subsequent investigation concluded that the death was not related to gene therapy . </P> <P> In 1972 Friedmann and Roblin authored a paper in Science titled "Gene therapy for human genetic disease?" Rogers (1970) was cited for proposing that exogenous good DNA be used to replace the defective DNA in those who suffer from genetic defects . </P>

When would a gene ever not be expressed