Gene Therapy

a. Introduction

Gene therapy is a technique used to treat or prevent genetically related diseases, whereby absent or faulty genes are replaced by functional genes. Such genes are crucial to bodily functions because defective ones cause an enzyme involved in genetic metabolism to be absent and give rise to genetic diseases. By using this technique, correct enzymes or proteins can be synthesized and thus remedying genetic disorders. While gene therapy is still in its early development, there are several approaches already used to correct genetic faults. 

Firstly, and the most common method, is the insertion of normal, workable genes into nonspecific locations within the genome in order to be swapped with defected ones. The next approach is similar to the first, the only difference being that the normal genes replace abnormal genes through homologous recombination. Thirdly is reverse mutation, where a faulty gene is selectively repaired to return it to its normal functional state. This last approach involves inactivating a mutated gene that is improperly functioning, or in other words, altering the regulation of a certain gene.

b. How it works? 

In most gene therapy studies, a "normal" gene is inserted into the genome to replace an "abnormal" disease-causing gene. Gene therapy depends upon vectors, which is a carrier molecule must be used to deliver the therapeutic gene to the patient's target cells or the defective gene. Currently, the most common vector is a virus, which is the most popularly retroviruses that have the capability of injecting their genetic material into the host cells that has been genetically altered to carry normal human DNA. This viral genetic material is armed with the correct gene and once it integrates with the host genome, all the cells resulting from cell division of the host cell will contain the copy of the correct gene in place of the defective one. Liposomes, adeno-viruses and using naked DNA are some other options for vectors that are being investigated to replace defective genes in organisms. Viruses have evolved a way of encapsulating and delivering their genes to human cells in a pathogenic manner. Scientists have tried to take advantage of this capability and manipulate the virus genome to remove disease-causing genes and insert therapeutic genes. 

In the future, gene therapy technique may allow doctors to treat a disorder by inserting a gene into a patient’s cells instead of using drugs or surgery. Nowadays, researchers are testing several approaches to gene therapy, including: 

· Replacing a mutated gene that causes disease with a healthy copy of the gene.

· An abnormal gene could be swapped for a normal gene through homologous recombination.

· The abnormal gene could be repaired through selective reverse mutation, which returns the gene to its normal function. 

· Inactivating, or “knocking out,” a mutated gene that is functioning improperly.

· The regulation (the degree to which a gene is turned on or off) of a particular gene could be altered.

· Introducing a new gene into the body to help fight a disease.


c. Types

Germ therapy can be classified into 2 different types:

* Germ line therapy

This type of gene therapy involves the modification of germ cells, otherwise known as gametes. This alteration will then be inherited by the future generation. With germ line therapy, genes could be corrected in the egg or the sperm that is being used to conceive. The child that results would be spared certain genetic problems that might otherwise have occurred. Because every cell is derived from the fertilized egg, every cell in the offspring would possess the transplanted gene. This would be a far more effective way of transferring genes than the ones presently used in somatic cell therapies, where genes into the cells of children or adults usually enter only a small portion of the person’s cells and eventually stop functioning. The idea of germline gene therapy is controversial. While it could spare future generations in a family from having a particular genetic disorder, it might affect the development of a fetus in unexpected ways or have long-term side effects that are not yet known. Because people who would be affected by germline gene therapy are not yet born, they can’t choose whether to have the treatment.

* Somatic gene therapy

It involves obtaining white blood cells from the patient and then introducing the normal genes into the cell. The normal gene is delivered using a domesticated retrovirus that infects the cell and introduces the normal functioning gene. Retroviruses are able to infect many types of cells, and therefore the development of gene transfer techniques is crucial so that will allow the viruses to deliver the genes to the cell and then remain there. It is imperative that the inserted gene gets to the intended gene location because an incorrect destination in the genome of the cell will certainly complicate matters and cause disastrous effects.

d. The Pros and Cons 

Gene Therapy Pros 

The most important factor that gives gene therapy its edge is its incredible therapeutic potential. Nowadays, the human race has always been under the continuous onslaught of diseases. As we find cure for some of the diseases, we are attacked by new and more virulent forms of germs. Although such diseases can be cured through medicines, genetic disorders have no cure unless the defective gene is replaced by the correct one and this is what the aims of gene therapy. Moreover, by targeting the reproductive cells, such defects can be got rid of for good. People suffering from genetic disorders like Parkinson's disease, Alzheimer's disease and Huntington's disease are some of those whose only hope for cure is gene therapy.

Gene Therapy Cons

Scientific Issues: Although the most popular choice as a vector, using virus for the purpose is not foolproof. There is a specific point within the host genome where the correct gene should be introduced. There is no guarantee that the viral enzyme that is responsible for this step will be able to introduce the correct gene at the specific point in the host chromosome. In case, there is an error in this process, it would result in error in the genetic makeup of the cell and can result in serious disorders. 

Moreover, the body's immune system may destroy the vector as it may perceive the carrier as a foreign body. Then there are problems with introducing therapeutic DNA and the rapidly dividing nature of certain cells that are hurdles in gene therapy providing long term benefits to patients. Due to this reason a patient may need to undergo multiple gene therapy treatments. But with this again comes the problem of the immune system. Once the immune system is triggered by a foreign body, it attacks the foreign body more aggressively when it invades the body next time. 

Ethical Issues: Given the technology involved, it is obvious that gene therapy treatment will be expensive. It will be just the rich who would be able to afford its benefits. This gives rise to the refrain that gene therapy will make the rich, richer and the poor, poorer. 

We know the potential of reproductive gene therapy. The scope of this line of treatment triggers the fear of eugenics - a term that denotes creation of a superior race, the idea that media has tried to embody in the concept of designer babies. Although this definitely isn't on the minds of geneticists but it is difficult to erase the repercussions of Hitler's belief in supremacy of the Aryan race.

Religious Issues: Manipulating genetic makeup of man is absolutely unacceptable by those with strong religious beliefs. According to them altering genes is similar to tinkering with nature. 

e. Summary

Undoubtedly, the therapeutic advantage of gene therapy is a blessing for mankind. However, unless the techniques of gene therapy are perfected, gene therapy pros and cons will keep fuelling the controversy. And also would this form of treatment be a luxury only for the rich which could very well make the rich, richer and make the poor, poorer. But should we deny mankind the blessings of a revolutionary scientific development that would bring an end to numerous incurable diseases? Be it industrialization or its harmful effects or the awesome source of power that nuclear energy is or its ugly face that we saw during the Hiroshima and Nagasaki bombings, man has been walking the tight rope of scientific developments and its ill effects. I do think that gene therapy could be a wonderful thing in curing series of diseases. But the costs of gene therapy would certainly be outrageous. Gene therapy could possibly be only for the rich and not the poor. The public needs to be more informed about the discoveries in gene therapy to aid in research. If the public is more willing to accept this, most of the scientists will discover more and better things. 

Group members:
Ding Kar Yong             1000923425
H'ng Kar Ching             1000820408
Qayyum bin Zainal        1000923740
Eileen Heng Ke Li         1000923357