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How is Gene Therapy Used to Cure Illnesses and Disorders?
Our chromosomes contain a lot of genes that encode proteins that our body needs in order to function normally, but they also contain genes that encode for proteins that cause us certain illnesses and disorders. In order to treat these genetic diseases, there has something to be done to replace or repair those genes so that they would not encode proteins that cause harm to our body. A process called gene therapy can be used to replace or repair those genes.
There are now different forms of gene therapy used to cure illnesses and disorders although the most common is the insertion of genes into a person's cells and tissues to replace defective genes. The replacement gene is delivered to the cells through the use of vector viruses. One of the most successful medical applications of this method so far is the treatment of X-linked severe immunodeficiency (X-SCID), a condition caused by adenosine deaminase deficiency. Retroviruses were used to deliver the right gene in the patients’ white blood cells to replace the faulty gene for adenosine deaminase.
There is also a form of gene therapy that alters the activation or inactivation of a particular gene by targeting transcription. For instance, you have a faulty gene that encodes a protein that causes the cell to divide abnormally; the goal is to prevent the transcription of this gene into messenger RNA so that there would no genetic translation or synthesis of the protein. One way to do this is by targeting proteins involved in genetic regulation called transcription factors.
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New Gene Therapy Activity
Transcription factors are proteins that bind to specific DNA sequences to needed. Depending on the needs of the body, transcription factors regulate the activation or inactivation of our genes.
There are times that transcription factors activate genes that mediate diseases in humans. The purpose of this form of gene therapy is to introduce double-stranded oligonucleotides (ODN) that bind to the promoter region of a gene. In this way, the transcription factor is blocked from attaching to the promoter region and the gene that mediates disease will not be transcribed. The ODN is delivered to the cells through the use of viral vectors. There are thousands of transcription factors in the body and some of them activate genes that cause diseases. Scientists are continuously identifying these transcription factors that could be targeted by double-stranded oligonucleotides so as to prevent the formation of diseases to our body.
Among the applications of ODN-based gene therapy is the prevention of lesion formation after vascular injury. ODN is used to inhibit the transcription factor E2F involved in the activation of genes for vascular lesion formation. The transcription factor NF-kB is also inhibited by ODN. NF-kB is involved in the activation of cytokine and adhesion molecule genes; activation of these genes is related to diseases like myocardial infarction and glomerulonephritis.
ODN-based gene therapy is still under clinical trial. In 1996, the FDA approved the use of ODN for the treatment of neointimal hyperplasia in vein bypass grafts. ODN targeted the E2F transcription factor, which activates genes for the formation of neointimal hyperplasia. Within a period of ten years, the clinical trial has a 50% success rate. That’s not bad but there are still unsettled issues on the clinical application of ODN including its susceptibility to nucleases, enzymes capable of cleaving oligonucleotides. More research is needed to improve ODN-based gene therapy so that in the near future it can be used to cure genetic illnesses and disorders in humans.
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Morishita et al. 1998. Application of Transcription Factor "Decoy" Strategy as Means of Gene Therapy and Study of Gene Expression in Cardiovascular Disease. Circulation Research of the American Heart Association Journals.