Gene therapy is a technique were DNA is used as therapeutic agent, that is mutated gene is replaced by functional gene to produce normal, functional proteins. Gene therapy can be used to treat both inherited disorders and acquired diseases. Inherited disorders like cystic fibrosis, haemophilia and acquired diseases like head and neck squamous cell cancer, glioma, Alzheimer's disease and lower limb ischemia can be treated using gene therapy.
Suicide Gene Therapy:
1. Suicide gene therapy uses herpes simplex virus thymidine kinase HSV-tk) gene with ganciclovir pro-drug
2. Cytosine deaminase (CD) gene is coupled with another pro-drug known as 5' fluirouracil (5-Fu)
3. Xanthine guanine phosphotransferase (XGPRT) gene is also used in desiging the vector
4. Purine nucleoside phosphorylase gene is also used in sucide gene therapy technique.
5. HSV-tk - gene has got the ability to phosphorylate broad range of guanosine analogues such as Ganciclovir, acylovir, buciclovir, penciclovor
6. Phosphorylation of guanosine induces the production of tumor necrosis factor-Î±, interlukin-6 and also interlukin-1Î±, this activates the cytotoxic T-cells and induces hemerogenic necrosis of the cell.
Advantages of Suicide gene therapy:
1. Cancerous cells or rapidly growing cells are more susceptible to impaired DNA synthesis, which in turn reduces the growth rate of these cells.
2. Gene therapy using HSV-tk/GCV has the ability to kill neighboring tumor cells
3. Tumor cells which are chemoresistant or drug resistant in nature can also be treated effectively using suicide gene therapy
Disadvantages of Suicide gene therapy:
1. Suicide gene therapy using HSV-tk technique enhanced growth, invasiveness, and chemotherapy resistance of tumor cells.
2. Clinical efficacy of suicide gene therapy is also limited by the low affinity of GCV towards HSV-tk
3. GCV inadequately transported into the cell and its phosphorylation level is also low, therefore GCV may not be the best substrate for HSV-tk
4. Effect and uptake of GCV is also varies depending upon the type of tumor cells
5. GCV uptake by the cell is also dependant on the expression of HSV-tk in the cell, that is if the expression of HSV-tk is low in the cell then the uptake of GCV will also decrease considerably
Future of Suicide Gene Therapy:
1. Cancer can be treated effectively by combining traditional chemotherapy, radiotherapy method along with suicide gene therapy technique.
2. Combining pro-drug therapy along with suicide gene therapy is also effective in treating tumor and cancer
3. Combining two or more genes can be used in suicide gene therapy
4. HSV-tk when combined with other genes also showed increased efficacy in killing tumor cell lines. Hence this technique can be used in suicide gene therapy to treat patients with cancer
5. HSV-tk genes when combined with other genes related to the immune system of human may also be used in suicide gene technique
6. Interesting characteristic of this technique known as suicide gene therapy is that different genes can be combined with HSV-tk/GCV therapy to get maximum efficiency to treat different types of cancer.
7. By considering all these points one can agree that suicide gene therapy is a promising solution to kill tumor or cancer cells
Suicide gene therapy is in its infancy stage, but at present a lot of research work is going on to improve the effectiveness of this technique used in treating different types of cancer. May be in coming few years all the limitations this technique will be solved and suicide gene therapy can become one of the most effective therapy to treat cancer and also other forms of tumors.
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