Short-lived nature of gene therapy:- For gene therapy to become a permanent cure, for any condition, the therapeutic DNA introduced into target cells must remain functional and the cells containing the therapeutic DNA must be long-lived and stable. Problem with integrating therapeutic DNA into the genome and the rapidly dividing nature of many cells prevent gene therapy from achieving any long term benefits. Patients will have to undergo multiple rounds of gene therapy.
Immune Response: Most of the virus used as a vector triggers production of immune cells against them and this can lead to early destruction of such viral vectors. Atimes, similar to organ transplantation, gene therapy has been plagued by the problem of immune rejection. So far, delivery of the normal gene has been difficult because the immune system recognizes the new gene as foreign and rejects the cells carrying it.
Remedy:- To overcome this problem the HSR-TIGET group in Molian Italy reported that this problem can be solved (Brown et al., 2006) by utilizing a newly uncovered network of genes regulated by molecules known as microRNAs which is a small non-coding RNA molecule found in plants and animal which functions in transcription and post transcriptional regulation of gene expression.
One of the researchers in Dr. Naldini ‘s group reasoned that they could use this natural function of micro RNAs to selectively turn off the identify of their therapeutic genes in cells of the immune system and prevent the genes from being found and destroyed. The researchers injected mice with target sequence, and the Mice did not reject the gene, as previously occurred when without the micro RNA target sequence were used. This work will have important implications for the treatment of hemophilia and other genetic diseases by gene therapy.
- Problem with viral vectors:- Viruses, the carrier of choice in most gene therapy studies, presents a variety of potential problem to the patient; toxicity, immune and inflammatory responses genetic control and targeting tissues. In addition, there is always the fear that the viral vector, once inside the patient, may recover its ability to cause diseases.
- Multi gene disorders:- Conditions or disorders that arise from mutation in a single gene are the best candidates for gene therapy. Unfortunately some of the most commonly occurring disorders such as heart disease, high blood pressure, alzheimer’s disease, arthritis and diabetes are caused by the combined effects of variations in many genes. Multi gene or multifactorial disorders such as these would be especially difficult to treat effectively using gene therapy although a 2013 trial using genes ins and GcK reported promise in treating diabetes in dogs (Callejas et al., 2013)
- Insertional Mutagenesis:- During integration of the therapeutic gene into the host genome, it may insert into the region of one of the genes regulating cell growth, for example, a tumor suppressor gene and this could induce a tumour or cancer. This has been observed in patients undergoing clinical trials for X-SCID, in which hematopoietic stem cells were transduced with corrective transgenes using a retrovirus, and this led to the development of T-cell leukaemia in 3 of 20 patients (Woods et al., 2006; Thrasher et al, 2006).
Remedy:- Many approaches are currently being evaluated to reduce the risk of viral vector-induced oncogenesis. These include;
- Deletion of the endogenous retroviral promoter to generate sequence in activating (SIN) vectors would reduce the probability of transactivation of a host gene following integration.
- The incorporation, in retroviral expression cassettes, of insulator DNA elements that shield genes from the effects of exogenous promoters would further reduce the possibility of host gene transactivation by the internal promoter.
- Development of vectors that integrate in specific and safe chromosome sites (Amit et al., 2004).
CONCLUSION AND RECOMMENDATION ON gene therapy
The knowledge for application of gene therapy arise with the emergence of diseases due to defect genes. These defect/mutated genes usually give rise to abnormal protein with abnormal function in human cell, thus in order to avoid the clinical consequences, associated with such diseases especially those that drugs do not provide a long-lasting solution, for example infant immunodeficiency, leukaemia and other cancers, there is need to use gene therapy for their treatment and cure. Gene therapy is usually of two types, Germ line and somatic which is the one mostly carried out in clinical trials.
Gene therapy is carried out using either the viral method or non-viral methods. Despite the early hindrances to gene therapy the technology has continued to lay an impact in treatment of most disease and currently many new clinical trial using gene therapy are being carried out in different parts of the world.
There are still some obstacles to the development of gene therapy for example; low efficiency, development of immune response against the therapeutic genes, insertional mutagenesis that may cause cancer, however efforts are being put in place to provide strategies that will help to overcome these problems, once they are abolished, the advantages of gene therapy cannot be over emphasized in treatment and cure of both genetic & acquired hematological disorder including other diseases.
Having seen the usefulness and challenges facing the adoption of gene therapy into medical practice I hereby recommend through this review that;
- Nigerian scientist should join their fellow colleagues or form research and groups that will contribute to final resolution and development of gene therapy using animal models to combat/ fight most of the genetic diseases that was previously though to be incurable.
- Once fully developed, government should enact a law that will allow the use of gene therapy as a lasting solution in treatment of certain diseases that have no other cure, example cancers, since chemotherapy are also destructive to normal cells and bone marrow transplantation also being very rare to find donors in addition with problem of graft versus host diseases.
- Universities authority should include gene therapy in their academic curriculum in order to widen students knowledge on the topic, so that they can contribute their own quota of understanding to gene therapy development as their counterparts in developed countries.