Genes are the smallest functional units present in the human body, which controls the development and formation of the organism. These genes are present on the chromosomes as pair and are expressed when the body needs a certain protein or compound. However, at times, one or both the genes may be faulty due to mutations. This impaired gene causes the formation of a Genetic disorder. These genetic diseases were studied with the tools of biotechnology and thus developed the Gene Therapy technique (Sheridan 121).
Gene therapy is a tool that uses biotechnological techniques to prevent diseases caused by defective genes. It has the potential to allow doctors to insert a gene in patients and treat the disease rather than to use drugs. However, that advancement is still for the future. There are few approaches developed by researchers for the gene therapy technique (Sheridan 122). They are:
- Replacement of the defective gene with a healthy copy of that gene
- Removing, i.e. knock-out the mutated gene which causes the genetic disorder
- Inserting a new gene inside the genome that treats the genetic disorder
There are two types of gene therapy depending of the cells on which they are used – somatic and germ line. In somatic gene therapy, the correct (therapeutic) gene is inserted in only the diseased cells of a patient. The modifications made and the effects are limited to the patients, and are not inherited by the patient’s children. Somatic gene therapy is topical and has to be done few times in a life time. On the contrary, in germ-line gene therapy, the therapeutic gene is inserted in the cells involved in reproduction (egg or sperm). This ensures that the corrective gene therapy is incorporated in the future generations as well. Even though germ-line gen therapy is effective against many hereditary disorders, it has been prohibited for human trials in countries like Australia, Canada, Germany, Israel, Switzerland, etc., due to the ethical and potential unknown risks reasons (Sheridan 123).
The basic idea of gene therapy is to insert a gene into the cells to compensate for the faulty genes. It causes the formation of correct proteins, which in the case of disorder were not being produced or were dysfunctional. However, these therapeutic genes cannot be just injected into the patient or in the cells. In gene therapy, tools of genetic engineering are used to delivery and the introduction of the therapeutic genes in the cells. These tools are called as ‘vectors’ (genetic vectors). There are viral and non-viral vectors used for gene therapy.
Viral vectors are commonly and most successfully used in gene therapy. Viruses attach themselves to the host cells and then incorporate their genetic material with the host cells, which are then further replicated in the host cells. In gene therapy, this property of viruses is used to insert the therapeutic genes in the diseased cells. The viral DNA is removed and thus a virus is used as a means of transport the therapeutic gene in the affect tissues. There are many viruses used in gene therapy, which includes retrovirus, adenovirus, lentivirus, herpes simplex virus, vaccinia, pox virus and adeno-associated virus. These viruses are genetically modified such that they do not cause any disease but act as mere vehicles of transport of genes by infecting the cells (Ferrua et al. 552).
Non-viral vectors are used because of its advantages over viral vectors. The primary advantages include large scale production of these vectors and their low host immunogenicity. The efficiencies of non-viral vectors were low, however, with new nanotechnology methods and recent advances in vector technologies the efficiency of non-viral vectors have been improved significantly. Commonly used non-viral vectors are electroporation, gene gun, sonoporation, magnetofection and the use of oligonucleotides, lipoplexes, dendrimers, and inorganic nanoparticles (Huang 1648).
Figure 1: Gene therapy with adenovirus. (Source: U.S. National Library of Medicine)
These vectors containing the corrective genes are injected intravenously (IV) in the affected tissue of the body, where it is incorporated in the human body. An alternate method is to extract patient’s cells and then exposed to the vectors in sterile laboratory conditions. The cells after the insertion of the therapeutic genes are then reintroduced in the patient. After the gene is introduced, the functional protein would be synthesized, and thus treat the disorder.
The application of gene therapy is majorly therapeutic. It is effective to combat not only genetic diseases but other disorders of faculty protein synthesis. The first FDA-approved gene therapy was treatment of ADA-SCID (Adenosine deaminase deficiency - Severe combined immunodeficiency). Since then gene therapy is used for treatment of X-linked SCID, Parkinson’s disease, multiple myeloma, Leber’s congenital amaurosis, adrenoleukodystrophy, chronic lymphocytic leukemia (CLL), acute lymphocytic leukemia (ALL) and haemophilia. The research for the application of gene therapy to various diseases is continuously being improved and understood. However, there are few areas that need to be addressed before the complete application of gene therapy. The researchers have to ensure that the best methods and vectors are available for gene transfer and the inserted genes are performing only as per the intended purpose (Fischer et al. 458).
Pros and cons
The benefits of gene therapy outweigh the problems associated with gene therapy. It is the best therapeutic technique for the treatment of a lot of genetic and non-genetic disorder. Some of the problems associated with gene therapy are:
- The gene therapy is not a permanent cure and is dependent on the stability and functionality of the gene introduced.
- The immune response of the human body against the foreign DNA can reduce the effectiveness of the inserted gene.
- The choice of vectors is crucial in gene therapy. These vectors should not induce any toxic, immune or inflammatory response and attack only the target tissues.
- Gene therapy today is effective against only a single gene disorder, and in multi-gene disorders like high blood pressure, Alzheimer’s, etc., gene therapy is yet to be developed.
- Other ethical and social issues include germ-line therapy, the misuse of gene therapy or its use in biological warfare. Therefore, the societal impacts of gene therapy need to be addressed by the Government through rigorous objectivity (Friedmann 948-949).
Gene therapy technique is being evolving with the understanding of science and technology. It has been used successfully, and would be developed further to address the issues that impede the application of gene therapy. As the use of this technology increases, the disabilities in the society would go on decreasing. The primary focus of this technology would be to correct the genetic flaws and reduce the life threatening diseases. Policies regarding the regulation of gene therapy are developed and are being evolved with the understanding of DNA regulation. In future, gene therapy would become easily accessible and simpler to answer even more complex problems of gene disorders.
- Ferrua, F., Brigida, I. and Aiuti, A. "Update on gene therapy for adenosine deaminase-deficient severe combined immunodeficiency". Current Opinion in Allergy and Clinical Immunology, (2010), 10 (6): 551–556.
- Fischer, A., Hacein-Bey-Abina, S. and Cavazzana-Calvo, M. "20 years of gene therapy for SCID". Nature Immunology, (2010), 11 (6): 457–460
- Friedmann, T. and Roblin, R. "Gene Therapy for Human Genetic Disease". Science, (1972), 175 (4025): 949–955.
- Huang, N., "Gene Therapy Progress and Prospects: Nonviral vectors". Gene Therapy, (2002), 9 (24): 1647-1653.
- Sheridan, C. "Gene therapy finds its niche". Nature Biotechnology, (2011), 29 (2): 121–128.