Adenosine Deaminase Deficiency (ADA disease) is one of the severe combined immunodeficiency ,which is type of disorder that affect the immune system. This disease are very rare and it lack of immune system and leaves body expose to bacteria without tough protection. This type of disease is fatal unless it should be corrected in some way. This disease are connected to the gene disease which inherited by both carrier parents which their autosomal chromosome that had been mutated and passed to their child. There is a lot of ways to cure this disease including the transfusion of blood from the high ADA donors. But there is a major problems due to this treatment which is a gene regulation. The blood have two alpha and beta chains. When one of the chain exceed thus it will causes the cell damages. Thus gene therapy is an alternative ways to cure this disease. Gene therapy is treating of genetic disorder like ADA disease by introducing into individual normal gene to replace or overcome the effect of mutated gene.
There is two type of gene therapy which is somatic cell therapy and germ-line cell therapy. Somatic cell is a treatment which is the genes are transferred into the somatic cells of a patient. Any modifications and effects will be experience by the individual patient only, and will not be inherited by the patient's child. The germ-cells is about the modification of germ cells example sperm or ovum by the introduction of functional genes which is integrated into their genomes and also this gene can be heritable to their offspring. But usually the somatic cell therapy is widely used to cure ADA disease rather than the germ-line because of this highly effective on countering the gene disease make the rise of ethical reasons. The somatic cells are modified genetically to prevent a genetic defect in off spring. It had shown successfully that ADA-corrected cells divide more faster rather than culturing white blood cells. But getting sufficient amounts of normal gene was not an obstacle. There is hundreds of human gene that had been isolate and characterized by the cloning and recombinant DNA technique. But the major obstacle was getting the DNA back into patients. The ways on how the ADA disease get cured was firstly the normal ADA from T-lymphocyte is separated and transplanted through the Retroviruses. Before that the part of the virus gene is replaced with normal human ADA gene which is needed to be transferred. When a retrovirus infects a host cell, it will introduce its RNA together with some enzymes, namely reverse transcriptase and integrase, into the cell.
This RNA molecule from the retrovirus must produce a DNA copy from its RNA molecule before it can be integrated into the genetic material of the host cell. The process of producing a DNA copy from an RNA molecule is termed reverse transcription. It is carried out by one of the enzymes carried in the virus, called reverse transcriptase. After this DNA copy is produced and is free in the nucleus of the host cell, it must be incorporated into the genome of the host cell. That is, it must be inserted into the large DNA molecules in the cell (the chromosomes). This process is done by another enzyme carried in the virus called integrase .Now that the genetic material of the virus is incorporated and has become part of the genetic material of the host cell, it can be said that the host cell is now modified to contain a new gene. If this host cell divides later, its descendants will all contain the new genes. Sometimes the genes of the retrovirus do not express their information immediately.One of the problems of gene therapy using retroviruses is that the integrase enzyme can insert the genetic material of the virus in any arbitrary position in the genome of the host- it randomly shoves the genetic material into a chromosome. If genetic material happens to be inserted in the middle of one of the original genes of the host cell, this gene will be disrupted insertional mutagenesis. If the gene happens to be one regulating cell division, uncontrolled cell division or cancer can occur. This problem has recently begun to be addressed by utilizing zinc finger nucleuses or by including certain sequences such as the beta-globin locus control region to direct the site of integration to specific chromosomal sites.
The viral-vector is then mixed and bred together with normal human cells in laboratory. The vector later enters the normal cells then forming new genes and stays permanently inside the chromosome. The new gene is known as virus-mediated gene.The transfer of the new virus-mediated gene into the T lymphocyte cell of ADA(-)SCID 's patient is done by intravenous injection. Therefore ADA(-) gene is now repairable so that it can returns to produce normal ADA enzyme. The repaired gene of T lymphocyte cells can live normally in the receiver's body. In fact it lives longer than the unrepaired T lymphocytes. Cell implant of the repaired gene should be done continuously once in a few months. Instead, if the gene therapy can be done to bone marrow stem cell, ADA(-)SCID children may be fully cured with only one treatment without the continuous need of new ADA gene implant.
