Gene Therapy Tries To Fix Disease Causing Gene Biology Essay

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Gene Therapy consists of trying to "fix"a disease-causing gene.Gene therapy is the insertion of genes into an individuals cell and biological tissue to treat diseases, such as cancer where deleterious mutant alleles are replaced with functional ones. Although the technology is still in its infancy, it has been used with some success. Scientific breakthroughs continue to move gene therapy toward mainstream medicine.Some genes cause disease because they are "broken" - so fixing them would require putting a nice new copy of the gene back in the cell. This is quite complicated, as the way each disease gene causes disease can be quite different.

Some diseases are caused by multiple genes and are more difficult to try to correct. Some genes cause disease because they are too "aggressive" - so fixing them would require removing or otherwise interfering with the "aggressive" gene. The immune system rejection and ensuring that the DNA that you are introducing will function inside the patient in question are also big hurdles. Gene therapy is the introduction of genetic material into cells for therapeutic purposes. Recent scientific breakthroughs in the genomics field and our understanding of the important role of genes in disease has made gene therapy one of the most rapidly advancing fields of biotechnology with great promise for treating inherited and acquired diseases. There is also a strong ethical component to the idea of gene therapy, especially on germ cells.

In general a gene cannot be directly inserted into a person's cell. It must be delivered to the cell using a carrier, or vector. Vector systems can be divided into:-

1. Viral vectors

2. Non viral vectors

Types of gene therapy:-

Gene therapy may be classified into the two following types:-

Germ line gene therapy:-

In the case of germ line gene therapy, germ cells, i.e., sperm or eggs, are modified by the introduction of functional genes, which are ordinarily integrated into their genomes. Therefore, the change due to therapy would be heritable and would be passed on to later generations. This new approach, theoretically, should be highly effective in counteracting genetic disorders and hereditary diseases. However, many jurisdictions prohibit this for application in human beings, at least for the present, for a variety of technical and ethical reasons.

Somatic gene therapy:-

In the somatic gene therapy, the therapeutic genes are transferred into the somatic cells of a patient. Any modifications and effects will be restricted to the individual patient only, and will not be inherited by the patient's offspring or later generations.

Vectors in gene therapy:-

Viruses:-All viruses bind to their hosts and introduce their genetic material into the host cell as part of their replication cycle. This genetic material contains basic 'instructions' of how to produce more copies of these viruses, hijacking the body's normal production machinery to serve the needs of the virus. The host cell will carry out these instructions and produce additional copies of the virus, leading to more and more cells becoming infected. Some types of viruses insert their genes into the host's genome, but do not actually enter the cell. Others penetrate the cell membrane disguised as protein molecules and enter the cell. Many human diseases are caused by the absence or inappropriate presence of a protein. Biotechnology's first promise was to isolate and produce these natural proteins through genetic engineering and recombinant technology. The protein could then be administered to patients in order to compensate for its absence. Because proteins are not orally available, biotech companies focused on innovative methods of protein delivery and sustained drug delivery. Today, gene therapy is the ultimate method of protein delivery, in which the delivered gene enters the body's cells and turns them into small "factories" that produce a therapeutic protein for a specific disease over a prolonged period. In summary, the distinction is that the results of any gene therapy is restricted to the actual patient and are not on to his or her children. All gene therapy to date on humans has been directed at somatic cells whereas germ line engineering in humans remains controversial and prohibited in for instance the European Union.

In vivo transfer viruses can be good:-

Placing a new gene into a patient is difficult; DNA, the material that makes up genes, cannot simply be swallowed like a pill or even injected into the blood. Unprotected DNA in the body will likely be broken down, and any surviving DNA may not effectively recognize or enter the target cells for absorption. The unprotected DNA-carrying the instructions for normal blood clotting-needs a vector, or carrier, to bring it into the correct cells in a patient's body. The most common vectors for gene transfer are viruses. DNA carrying the factor VIII gene is first combined with DNA from a virus that is capable of quickly finding and infecting certain cells-delivering normal DNA into the right cells.


The genetic material in retroviruses is in the form of RNA molecules, while the genetic material of their hosts is in the form of DNA. When a retrovirus infects a host cell, it will introduce its RNA together with some enzymes, namely reverse transcriptase and integrase, into the cell. This RNA molecule from the retrovirus must produce a DNA copy from its RNA molecule before it can be integrated into the genetic material of the host cell. The process of producing a DNA copy from an RNA molecule is termed as reverse transcription. It is carried out by one of the enzymes carried in the virus, called reverse transcriptase. After this DNA copy is produced and is free in the nucleus of the host cell, it must be incorporated into the genome of the host cell.

The Fundamentals of gene therapy:-

Curing haemophilia through gene therapy means correcting a person's genetic defect by placing non-defective, normal functioning genes into his cells. Normal factor VIII or factor IX genes would be inserted into enough cells to enable a person to continuously make enough factor to "cure" his Haemophilia. This challenge was answered by the many drugs companies and research labs developing recombinant drugs, such as insulin, growth hormones, interferon and factor VIII; and by scientists doing basic research in genetic engineering. While the basic techniques for moving genes from one cell to another are now easily performed, a successful gene therapy program demands much more than these and has some very specific requirements:

1. The gene being transferred must be put into cells where it will function normally and

2. Once transferred, the gene should function in the cell for a long time, preferably indefinitely. Either the cells with the new gene, called transduced cells, must themselves survive for a long time, or they must be able to pass the gene on to future generations of cells. It doesn't serve much purpose to put this gene into cells that are going to die in a short time.

3. The newly transferred genes, called transgenes, must be properly expressed-thatis, they must produce enough factor for adequate blood clotting.

4. The gene transfer must not damage normal DNA. If the gene is introduced randomly into DNA, other genes may be disturbed, or normally quiet genes may be "turned on," potentially leading to cancer or other aberrant cell changes. The goal is to add one new function-making factor-without altering any of the cell's other functions.

5. The gene transfer should not lead to any immune reaction that limits the gene's effectiveness, prevents future treatments, or causes serious side effects.

6. The transfer process must be consistent from person to person, relatively simple to perform, and successful with all persons with haemophilia. These requirements for a successful haemophilia gene therapy program centre on two key medical issues: safety and efficacy. Safety refers to minimizing injury or damage to a patient, and efficacy refers to how well a patient's blood will clot.

Gene therapy stops blood disorder, Ending Need for Transfusions:-

A 21-year-old man with a blood disorder who needed monthly transfusions to survive since he was 3 had his condition halted by a gene therapy procedure. The man suffered from beta thalassemia, a common genetic disease that reduces red blood cell production. Bluebird, backed by four venture capital firms and Genzyme Corp, the world's largest maker of drugs for rare genetic diseases, plans to treat nine more patients who have thalassemia or sickle cell anaemia.

Gene doping:-

Gene therapy for restoring muscle lost to age or diseases is poised to enter the clinic , but athletes are eyeing it to enhance performance. The non-therapeutic use of cells, genes, genetic elements, or of the modulation of gene expression, having the capacity to improve athletic performance is defined as Gene Doping.

Gene Doping Detectable With a Simple Blood Test:-

German scientists from Tubingen and Mainz have developed a blood test that can reliably detect gene therapy even after 56 days. Scientists at the universities in Tubingen and Mainz have developed a test that can provide conclusive proof of gene doping. "For the first time, a direct method is now available that uses conventional blood samples to detect doping via gene transfer and is still effective if the actual doping took place up to 56 days. But viruses are good candidates for the role of vector because they are structurally simple, usually consisting of small pieces of DNA, RNA and a few proteins. They are also fairly easy to study, can be genetically altered, and have a natural tendency to attach to specific cell types and transfer their DNA into those cells.

How is Gene Therapy done?

To get a new gene into a cell's genome, it must be carried in a molecule called a vector. The most common vectors currently being used are viruses, which naturally invade cells and insert their genetic material into that cell's genome. To use a virus as a vector, the virus' own genes are removed and replaced with the new gene destined for the cell. When the virus attacks the cell, it will insert the genetic material it carries. A successful transfer will result in the target cell now carrying the new gene that will correct the problem caused by the faulty gene. The actual transfer of the new gene into the target cell can happen in two ways: ex vivo and in vivo. The ex vivo approach involves transferring the new gene into cells that have been removed from the patient and grown in the laboratory. Once the transfer is complete, the cells are returned to the patient, where they will continue to grow and produce the new gene product. The in vivo approach delivers the vector directly to the patient, where transfer of the new gene will occur in the target cells within the body. Viruses that can be used as vectors include retroviruses like HIV, adenoviruses (one of which causes the common cold), adeno-associated viruses and herpes simplex viruses. There are also many non-viral vectors being tested for gene therapy uses. These include artificial lipid spheres called liposomes, DNA attached to a molecule that will bind to a receptor on the target cell, artificial chromosomes and naked DNA that is not attached to another molecule at all and can be directly inserted into the cell.


While the transfer of the new gene into the target cells has worked, it does not seem to have a long-lasting effect. This suggests that patients would have to be treated multiple times to control the condition or disorder. There is also always a risk of a severe immune response, since the immune cells are trained to attack any foreign molecule in the body. Working with viral vectors has proven to be challenging because they are difficult to control and the body immediately recognizes and attacks common viruses. Before gene therapy can be used to treat a certain genetic condition or disorder, certain requirements need to be met:-

The faulty gene must be identified and some information about how it results in the condition or disorder must be known so that the vector can be genetically altered for use and the appropriate cell or tissue can be targeted.

The gene must also be cloned so that it can be inserted into the vector.

Once the gene is transferred into the new cell, its expression (whether it is turned on or off) needs to be controlled.

There must be sufficient value in treating the condition or disorder with gene therapy - that is, is there a simpler way to treat it?

The balance of the risks and benefits of gene therapy for the condition or disorder must compare favourable to other available therapies.

Sufficient data from cell and animal experiments are needed to show that the procedure itself works and is safe.

Once the above are met, researchers may be given permission to start clinical trials of the procedure, which is closely monitored by institutional review boards and governmental agencies for safety.

One promising application of gene therapy is in treating type I diabetes. Researchers in the United States used an adenovirus as a vector to deliver the gene for hepatocyte growth factor (HGF) to pancreatic islet cells removed from rats. They injected the altered cells into diabetic rats and, within a day, the rats were controlling their blood glucose levels better than the control rats. This model mimics the transplantation of islet cells in humans and shows that the addition of the HGF gene greatly enhances the islet cells' function and survival. Pancreatic islet cells are then injected through the catheter into the liver. In time, islets are established in the liver and begin releasing insulin. Another application for gene therapy is in treating X-linked severe combined immunodeficiency (X-SCID), a disease where a baby lacks both T and B cells of the immune system and is vulnerable to infections. The current treatment is bone marrow transplant from a matched sibling, which is not always possible or effective in the long term.


Gene addition seeks to compensate for a defective gene (red) by providing cells with a corrective gene (green).

Genes can be injected directly into cells or they can be coaxed in by chemical or electrical means.

Most delivery systems deposit corrective genes in the cell's nucleus, where it remains only transiently,

Other methods integrate genes into the chromosomes. Integrated genes can be passed on to progeny.

Virus delivery: Viruses can be used as gene delivery vectors.

Viral genes targeting the cell's nucleus are retained in the vectors , while harmful viral are removed and replaced with the corrective gene. Some viruses integrate corrective genes into chromosomes, but randomly.

Replacement Therapy:-

How Long Can a Person Be "Cured" by Gene therapy?

So far the "success" of gene therapy programs has been short-lived; in one case, a dog with Haemophilia was "cured" for about 30 days, but Haemophilia symptoms returned. For a person to be cured for years-or permanently-two things must happen: 1) the transferred gene must remain stable and functioning within the cells; and 2) the cells themselves must remain functioning. 3) More recent studies have improved clotting function in haemophilic animals for many months (dogs) or the lifetime of the animal (mice).

Risks of Gene Therapy:-

The most obvious risk of gene therapy is that the viral vectors will act like viruses-they may keep, or recover, their ability to cause infections. Fortunately, most of the viral vectors under investigation either do not cause disease in humans, or have been genetically rendered harmless. Most vectors are being modified further, both to increase their effectiveness and to add levels of safety against any unwanted viral activity. A second, more complex risk is that gene therapy will stimulate a person's immune system in a way that either decreases the effectiveness of the therapy, or makes it difficult to perform future therapy. Our immune systems are designed not only to attack "foreign" objects.

Current Programs in Gene Therapy:-

The good news for people with haemophilia and their families is that numerous research labs are trying to develop gene therapy methods for treating haemophilia, and studying the biochemistry of clotting factors. This work will undoubtedly lead to a more thorough understanding of how gene therapy can cure haemophilia.

Gene Therapy's Future :-

Gene therapy has not advanced as quickly as many scientists predicted, yet there has been constant progress, and so far no obstacles appear insurmountable. However, it is the complexity and specificity of the gene therapy process that makes it so difficult to achieve: the goal is to make one, and only one, unique change in a person's genetic and metabolic make-up. Gene therapy holds great promise as a lasting cure for haemophilia. But, the advent of recombinant factor products, improvements in technology do not necessarily mean improved access for many of the world's haemophilia patients.