Interview

Gene 'tricks'

Though gene therapy is being touted as a potential cure for dreaded diseases like cancer and diabetes, research is still at a very preliminary stage. Dr Rita Mulherkar, Head, Genetic Engineering, Advance Center for Treatment Research and Education in Cancer (ACTREC), Tata Memorial Center, speaks to Sachin Jagdale about the recent developments in this area

What is gene therapy and how does it work?

Gene therapy is the use of genes or DNA to treat a disease just like a drug. The therapeutic gene has to enter the nucleus of the cell and start synthesising the protein which has a role to play in the disease. For example, if a person is suffering from hemophilia and does not make enough of the blood coagulating factor protein, a gene which makes the factor can be put into the patient's cells so that it will make protein which will help in blood coagulation.

What is the current status of research on gene therapy?

It is still in the experimental stage. Like any new drug which comes into the market, it has to undergo Phase I, II and III clinical trials before it can be sold in the market. The only gene therapy product which is in the market today, which is for cancer, is being marketed in China.

What are the factors that are holding back gene therapy from becoming an effective treatment for genetic diseases?

For a gene to express itself and make a protein, it requires certain regulatory DNA sequences, which are known as promoters and enhancers. We do not have sufficient knowledge about the regulatory sequences to make a therapeutic gene express just like the natural gene. Long term and controlled expression of the gene is required for genetic diseases. However, gene therapy has been successful in some genetic disorders such as severe combined immuno-deficiency disorder.

What are the recent developments in gene therapy research?

Efficient and safe viral and non-viral vectors are being developed and great progress has been made in this area. Also, means of transferring transgenes to early progenitor cells are being tested so that the gene remains in the body for longer time than when inserted in mature cells, which have a short life span.

What are the ethical issues that are associated with gene therapy?

Of course there are many ethical issues concerned with the use of gene therapy. The therapeutic gene should not pass from the patient to other individuals. It should not go into the germ cells of the patient as this could lead to germline transmission of the transgene. The most popular vectors used to carry the gene into the cell are viral vectors. Although the viruses are disabled and are made non-pathogenic by removing some of the viral genes, these issues, though rare, have to be answered in the animal models.

Proper clearances have to be obtained from biosafety and recombinant DNA regulatory committees. Before doing any studies in human subjects the protocols are scrutinized rigorously by Hospital Ethics Committees.

What are the target areas for gene therapy?

If you mean diseases - cancer is at the top of the list. Cardiovascular diseases, infectious diseases, neur-ological diseases are also good candidates for gene therapy.

Can we use gene therapy to make 'designer' humans?

No. So far in humans, gene therapy is permitted to be carried out only in somatic cells and not in germline cells.

How do gene therapy trials get approval?

Before going for clinical trials, one has to do extensive preclinical studies in the lab - on cell lines and animals to check safety and efficacy of the therapy. Then the reports are presented to a committee of experts in recombinant DNA technology and ethics committees in the institute. Once approval is obtained from the local regulatory bodies it has to be approved by the national regulatory bodies. The FDA equivalent has to give the final approval.

Don't you feel that sometimes gene therapy may become 'nature versus nature' debate?

No. Man is an intelligent animal. If man can use his intelligence to cure some of the dreadful diseases using gene therapy, there is nothing wrong in it. If this technology is misused for eugenics then it will be sad.

What efforts have been taken to make gene therapy safer?

Safety is one of the main concerns for any gene therapy. There is a lot of research going on to make the vectors carrying the transgene safer so that there are no side effects. Even the virus which causes AIDS is being tried as a vector for gene therapy since it is very efficient in transferring the gene to the target cells. These viruses are made non-pathogenic by removing the harmful genes from their genome and carrying out other alterations.

What kind of advancements are on the radar in gene therapy?

We have learnt a lot from the ongoing Phase I clinical trials based on which scientists are modifying their vectors as well as the transgenes which can be used for gene therapy. Also there is a plethora of information on the molecular biology of the disease which is helping scientists to use different targets for gene therapy.

sachin.jagdale@expressindia.com