Gene Therapy - Research Paper Example

Gene Therapy: Problems and Solutions to Problems Gene therapy is a method of treating various acquired and genetic diseases with genes. This is an experimental technique and is done by inserting genetic material into the patient’s cells. In this form of treatment, the diseases are either treated or prevented by replacing abnormal gene, or by introducing the absent gene or by supplementing the defective gene (Genetics Home Reference, 2008). The genes thus introduced exert their benefits by either compensating for the abnormal genes or by producing beneficial protein or by supplementing the abnormal gene (Hecht, n. p.).

The first gene therapy clinical trial started in 1990 (Verma and Weitzman, n. p.). Currently, research is going on for gene therapy by various approaches in different parts of the world for various diseases like combined immune deficiencies, hemophilia, Parkinson's disease, cancer and even HIV (Verma and Weitzman, n. p.). Though gene therapy has been under research for the past 2 decades, no single gene therapy has been approved for clinical use. The main reason for this is safety concerns pertaining to gene therapy trials and treatment.

In this essay, problems associated with gene therapy and strategies to prevent those problems will be reviewed. Safety issues related to gene therapy are mainly related to the methods employed in gene therapy. There are basically 2 methods of gene therapy and they are ex-vivo therapy and in-vivo therapy. In ex-vivo therapy, gene delivery is done in cells after being removed from the body (Hecht, n. p.). The cells used are basically grown in the laboratory. The cells are than modified outside the body and then transplanted back into the body.

In some research trials, cells from blood or born marrow are taken out and cultured in a laboratory. Thereafter, the cells are exposed to the virus with the desired gene. The virus infects the cells and transfers the therapeutic genetic material into the nucleus of the cells. After this, the cells are injected into the patient’s body by vein. In vivo therapy, gene delivery is being done in the cells that are still in the body. The genetic material can be delivered by different routes. The specific route is determined by the disease.

Gene therapy for cystic fibrosis is administered by inhalation. In hemophilia and cancer treatment, the gene is directly injected into the tumor (Hecht, n. p.). Viral vectors can introduce toxicity, immune and inflammatory responses. Also, though the viruses are engineered to be innocuous, there is always a fear that they may cause disease (Hecht, n. p.). Immunogenicity is an important factor with regard to safety of the patient subjected to gene therapy trial. The immunogenicity is that of the vector and it is derived from the proteins of the virus and the capability of the viruses to infect macrophages and dendrite cells.

Such an immune response can result in elimination of the transduced cells and also the vector (Hecht, n. p.). The potency and dose are very important aspects for good outcomes in gene therapy and these are basically linked to the production process and also the purification process (Raty et al., n. p.). These processes maximize the infective virus and decrease the number of defective viruses or empty viral particles. Using administration methods to increase the concentration of the virus locally helps in decreasing the side effects and also aids in lowering the amount of total dose that is administered into the patient.

In the ex-vivo approach, cells of the patient that are outside the body like skin can be used for transduction for augmentation of the grafting of the tissue and also for providing therapeutic protein secretion. These methods help in limiting the exposure to the patient to vectors of gene delivery, thus increasing safety aspects. These methods are however, laborious. Another method of decreasing the amount of dose administered to the person is by combining lipoproteins of low density with avidin (Raty et al., n. p.). In this method, substances that are bitinylated are captured to the cells from the circulation, thus effectively increasing the drug concentration locally.

This helps in reducing the side effects by limiting the amount of drug concentration in other tissues. Certain tissue specific promoters when used with gene therapy vectors along with promoters that can be regulated can help in decreasing the amount of vectors exposed to the body. Another strategy is to delete the replication genes in the vector, mostly adenovirus, so that the viruses are gutless. Currently third generation vectors are being used which are much safer. Improvement in chromatographic methods have decreased the purification of viruses and also the delivery of reservoirs like silicon collars or collagen collars which decrease systemic leakage of viruses along with tissue specific promoters.

Imaging the bio-distribution of particles of virus can help in gene therapy specificity, thus improving safety aspects (Raty et al., n. p.). To summarize and conclude, introduction of genetic material into the cells for therapeutic purposes is known as gene therapy. This mode of treatment is useful for diseases with gene absence, mutation or insufficiency. However this is still in experimental stage. Gene therapy offers hope to those with incurable genetic disorders, but is fraught with several challenges and side effects.

Improvement in the chromatographic methods has enhanced the purification of viruses and also the delivery reservoirs. Other strategies which can reduce harm due to gene therapy viruses are using of tissue specific promoters and also imaging of the viral bio-distribution. Works Cited Hecht, F. “Gene Therapy - The Future Is Here!” MedicineNet.com. 2004. Web. 10th May, 2013 . Raty, J.K., H. P. Lesch, T. Wirth, and S. Yla-Hertuala. “Improving Safety of Gene Therapy.” Current Drug Safety, 3, 46-53. 2008. Print.

Genetics Home Reference What is Gene Therapy? 2008. Web. 10th May, 2013 . Verma, I.M., Weitzman, M.D. “Gene Therapy: Twenty-first Century Medicine.” Annu Rev Biochem, 74, 711-38. 2005. Print.