Somatic cell gene therapy

In somatic cell gene therapy, a DNA sequence is inserted into a somatic cell to correct a mutation. Cells may be removed from the patient for manipulation and subsequent reinsertion (ex vivo therapy), or they may be manipulated without removal fi om the patient (in vivo therapy). Ideally, cells with a very long life span (e.g., bone marrow stem cells) are treated, but other cells (e.g., lymphocytes) are sometimes more practical targets. 

Somatic cell gene therapy involves the use of recombinant DNA techniques to introduce a therapeutic DNA sequence into a somatic (noninherited) cell. 

Currently, more than 400 human somatic cell gene therapy protocols are being tested. Most of these involve the use of genetically modified cells to treat noninherited diseases. For example, normal copies of the p53 tumor suppressor gene are inserted into lung tumors to halt tumor progression, and genetically modified cells have been used to create new coronary vessels in patients with coronary heart disease. Success has also been achieved in the treatment of hereditary disease (most notably, the recent successful treatment of X-linked severe combined immune deficiency see Clinical Correlate). 

Gene therapy is used to correct the effects of a disease-causing mutation. Somatic cell gene therapy is used in humans because the alteration is not transmitted to offspring. Germline gene therapy (not practiced in humans) alters all cells in the body and results in transmission of the alteration to offspring. 

The investigators evaluated the safety of their nonviral somatic-cell gene therapy system, which they call transkaryotic implantation, in six patients with severe hemophilia. The procedure involved isolation of dermal fibroblasts from the patients upper arms. The fibroblasts were then transfected with a factor VIII genebearing plasmid. Cells that expressed factor VIII were cloned, propagated, and implanted into the patients abdomens. This technique can be considered as a less invasive form of ex vivo gene therapy. 

An in vivo model of somatic cell gene therapy for human severe combined immunodeficiency. Ferrari, G., Rossini, S., Giavazzi, R., Maggioni, D., Nobili, N., Soldati, M., Ungers, G., Mavilio, F., Gilboa, E., Bordignon, C. (1991). Science, 251 (4999) 1363-1366. 

See gene inherit somatic cell gene therapy germ line gene therapy. 

See genomics somatic cell gene therapy, germ line genetic mutation. See mutation. 

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