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Home » Biology Homework Help » Biotechnology » Augmentation Therapy
Augmentation Therapy
In this type of somatic cell gene therapy, the functional gene is introduced in addition to the defective gene endogeneous to the cell(s) i.e. the modified cells contain both the defective (endogeneous) as well as the normal (introduced) copies of the gene. There are two general approaches to augmentation therapy. The first approach was used in the first two patients on whom gene therapy was attempted to correct the genetic disorder called Severe Combined Immune Deficiency (SCID) syndrome produced by adenosine deaminase (ADA) deficiency. (i) Normal ADA gene copies were produced by cloning and then (ii) packed into a defective retrovirus; most of the viral genes were replaced by the ADA gene. (iii) Lymphocytes were isolated from the patients, and (iv) the recombinant retroviruses were used to infect the lymphocytes. Finally, (v) the infected cells expressing the ADA gene were injected back into the patients. The normal ADA gene was expressed in the patients, and ADA deficiency was partially corrected, this resulted in an improvement in the patient’s immune system.

A variety of viral vectors have been used to deliver genes into target/stem cells, e.g. lymphocytes, bone marrow cells, cultured in vitro. The stem cells themselves are obtained either from the concerned patient (more desirable) or from a matched donor. The reservations about safety of retroviral vectors is sought to be solved by developing suicide vectors which cannot replicate after delivery of the gene. The other main problems of this approach are: (i) low frequency of transfection of stem cells, (ii) stability of the integrated gene, (iii) duration of the gene expression, (iv) lack of proper regulation of gene expression etc. More recently, interest has focused on physical methods of gene delivery like Ca2+ phosphate coprecipitation, particle gun, electroporation etc.

The second approach is the direct injection of DNA into the tissues either as protein complexes (in order to bring about receptor-mediated transfer of DNA into a specific tissue, e.g. liver) or even as naked DNA into muscle or skin. Interestingly these cells take the DNA and express the gene product. Exciting results have been obtained with experimental familial hypercholesterolemia, where LDL receptor levels have been augmented by injection of the gene as a sialoglycoprotein complex. The problems in this approach as well, relate to the frequency of cells taking up and expressing the gene and, more particularly, the duration of expression.

The gene delivery methods used for gene therapy can also be used for treatment of cancer or AIDS. In case of cancer, a toxin encoding gene can be delivered into the cancer cells. Similarly, appropriate interleukin genes can be delivered to boost the body’s defence mechanisms (in case of AIDS).

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