How Does Gene Therapy Work?

Original Paragraph

Gene delivery is one of the biggest challenges to successful gene therapy. You can imagine it would be hard to actually inject these genes into the tiny cells, so a carrier, or a "vector," is used to accomplish this. Typically, viruses are used as the vectors.  The virus vector must be genetically altered to carry human DNA. These viruses are like those that cause the common cold, only they are "deactivated" so that they will not cause the patient to actually get the cold. In some cases, some cells are taken from the patient and the virus is exposed to the cells in the laboratory. The virus with the desired gene attached finds its way into the cells. These cells are allowed to grow in the laboratory, and are then given back to the patient by intravenous (IV) infusion or are injected into a body cavity (i.e. the lung) or a tumor. In other cases, the vector with the attached gene is directly inserted into the patient by intravenous infusion or is injected into a body cavity or a tumor.  Once the gene has reached the cell, it must go to the cell's nucleus and become integrated within the human genetic material. Then it needs to be "turned on," to produce the protein product encoded by the gene. For gene delivery to be successful, the protein that is produced must function properly.

Gene therapy is still experimental, so the means by which it is given may change as the technology develops. 

Key Ideas: 

- A carrier, also known as vector is used to inject genes into the tiny cells

- Viruses are used as the vectors, it is genetically altered to carry human DNA

- The virus with the desired gene attached finds its way into the cells

- Gene therapy is still experimental, so the means by which it is given may change as the technology develops

Source: 

"Gene Therapy: The Basics." Cancer Resources. N.p., n.d. Web. 16 Oct. 2014. <http://www.oncolink.org/treatment/article.cfm?c=15&id=323>.

Paraphrasing:

For gene therapy to become a revolutionary breakthrough for mankind, we must first invent a way for gene delivery. Researchers have discovered a particular method that utilizes carriers or "vectors" where the genes are kept and given to the patient's body. Certain viruses act as vectors, in which the virus is genetically engineered and its "bad" DNA is deactivated as to contain un-harmful human DNA. There are two ways for a virus vector to infect an infected cell. The first method is by exposing the virus to the cell outside the body. The cells of the patient are extracted and brought into a laboratory, where in it comes in contact with the virus vector. Once the new gene has infected the defective cells, it is returned back to the patient. In contrast, the second method is directly placing the virus vector into the patient's body. The gene will manage on its own to find the infected cell, where it will have to go to the cell's nucleus then become united within the human DNA. Once done, it needs to be activated, thus producing the needed protein. For the cell or vector to be inserted into the patient's body, doctors utilize intravenous infusion or injection into a body cavity or a tumor. Using this particular method for gene therapy might not be the only one, as gene therapy is still undergoing research, thus future developments will possibly invent other techniques. 

Figure 2: Using vectors to transfer new healthy genes to the cells in the body
http://ghr.nlm.nih.gov/handbook/therapy/procedures

More Into Gene Therapy

Prospects for gene therapy

Several methods are now available for introducing new genetic material into mammalian cells. These methods allow consideration of a more direct approach to treatment of genetic diseases, namely, gene therapy or introduction of a functional gene to replace or supplement the activity of a resident defective gene. Typically, two strategies have been considered, germ-line and somatic cell gene therapy, which differ in the nature of the recipient cells. In the germ-line model, foreign DNA is introduced into the zygote or early embryo with the expectation that the newly introduced material will contribute to the germ line of the recipient, i.e., be passed on to the next generation. By contrast, in somatic gene therapy models, genetic material is introduced only into somatic cells and is not transmitted to the germ cells.

Key ideas:

-       Germ-Line Gene Therapy

-       Somatic Cell Gene Therapy

Source:

Fauci, Anthony S. Harrison's Principles of Internal Medicine, 14th Edition. New York: McGraw-Hill, Health Professions Division, 1998. Print.

Paraphrasing:

Gene therapy is the process of introducing healthy genes into the human body, or other mammalian beings. The treatment mainly focuses on genetic diseases by making a defective mutated gene come in contact with a healthy functional gene as to alter the resulted proteins of the gene that is the main source of the disease.

This treatment has two different approaches, they are known as the germ-line gene therapy and somatic cell gene therapy. The germ-line gene therapy targets gametes cells in the gonad organs. It enables healthy functional genes to be injected into either the zygote or an early embryo as to, hopefully cure the patient, as well as pass it down to their offspring and other future generations. On the other hand, the somatic cell gene therapy targets the other cells of the body. As it does not include sex cells, it has no possibilities of passing down the changes to their children or further generations.

The Clotting Problem Of Hemophilia

Original Paragraph: 
1. Blood is carried throughout the body within a network of blood vessels. When tissues are injured, damage to a blood vessel may result in leakage of blood through holes in the vessel wall. The vessels can break near the surface, as in a cut. Or they can break deep inside the body, making a bruise or an internal hemorrhage.

Platelets are small cells circulating in the blood. Each platelet is less than 1/10,000 of a centimeter in diameter. There are 150 to 400 billion platelets in a normal liter of blood. The platelets play an important role in stopping bleeding by clumping together and forming a plug, thereby beginning the repair of injured blood vessels. Clotting factors like factor VIII and IX are then needed to glue the plug in place thus forming a clot.

When one of the proteins, for example, factor VIII, is absent, the dominos stop falling, and the chain reaction is broken. Clotting does not happen, or it happens much more slowly than normal. The platelets at the site of the injury do not mesh into place to form a permanent clot. The clot is 'soft' and easily displaced. Without treatment, bleeding will continue until the pressure outside the broken vessel is equal to the pressure inside. This can take days and sometimes weeks.

2. Hemophilia is a family of clotting disorders. Most patients born with hemophilia are not able to form blood clots efficiently. Any modest injury can trigger excessive bleeding that can endanger life. Patients with severe hemophilia experience life-threatening spontaneous bleeds, unrelated to trauma. Some patients have a mild form of the disease in which a minor injury is not critical, but major trauma, such as car accidents and surgery, pose a significant risk.

Hemophilia is caused by mutations in one of the proteins involved in blood clotting (predominantly Factor VIII or Factor IX). Most patients, roughly 85%, have Hemophilia A and produce too little or no Factor VIII. Factor VIII is a relatively large protein and mutations occur as large deletions (6%), point mutations (43%), or as inversions in which part of the DNA is flipped backwards (intron 22A, intron 1). Patients with Hemophilia B have a defect in their Factor IX gene, such as deletions of variable length or point mutations. Patients with mild hemophilia maintain low levels of the clotting factor (5%-40% of the normal level in blood).

Key Ideas: 
- Platelets are small cells circulating in the blood, these platelets play an important role in stopping bleeding by clumping together and forming a plug
- Clotting factors like factor VIII and IX are then needed to glue the plug in place thus forming a clot
- When one of the proteins is absent, the chain reaction is broken. 
- Without treatment, bleeding will continue until the pressure outside the broken vessel is equal to the pressure inside. This can take days and sometimes weeks
- Hemophilia is a family of clotting disorders
- Patients with severe hemophilia experience life-threatening spontaneous bleeds, unrelated to trauma
- Patients have a mild form of the disease in which a minor injury is not critical, but major trauma, such as car accidents and surgery, pose a significant risk.
- Hemophilia is caused by mutations in one of the proteins involved in blood clotting
- There are two kinds of Hemophilia: Hemophilia A and Hemophilia B

Source:

1. "The Clotting Problem in Hemophilia." - Canadian Hemophilia Society. N.p., n.d. Web. 8 Oct. 2014. <http://www.hemophilia.ca/en/bleeding-disorders/hemophilia-a-and-b/the-clotting-problem-in-hemophilia/>.

2. "Hemophilia." ASGCT. N.p., n.d. Web. 8 Oct. 2014. <http://www.asgct.org/general-public/educational-resources/gene-therapy-and-cell-therapy-for-diseases/hemophilia>.

Paraphrasing: 

Hemophilia is an inherited disease that prevents the patient from forming blood clots effectively. People who are not infected with hemophilia have a normal way of recovering. When their tissues in the body, both inside and outside, are injured and damaged, blood vessels might get injured as well, thus the blood is exposed and leaks out from the hole of the cut, bruise or internal hemorrhage. When people experience being injured, the platelets that flow in the blood are extremely essential cells that are required to cluster and cover the hole of the injury, enabling the blood to stop flowing out.

However when one has hemophilia, injuries may result to continuous bleeding that can possibly be detrimental to one’s life.  The patient may experience one of the two effects. The first being life-imperiling bleeding injuries that have no relation to traumas, and the other being light forms of the disease with non-critical minor injuries, however major traumas may occur that highly risks the patient’s well being, in which these include car accidents and surgery.

In addition, for a patient to have hemophilia means to have a gene mutation in their body. In other words, the proteins responsible for blood clotting must have experienced substitution, inversion, deletion or insertion. Blood clotting proteins of Factor VIII and IX are predominantly the factors that were mutated. Estimated to be around 85% of the Hemophilia patients are infected with Hemophilia A, in which the body produces too little or no Factor VIII. Mutations of this particular factor are 6% due to large deletions, 43% due to substitution or 51% due to inversions. On the other hand, Hemophilia B is a case where in the patient has a flaw in their Factor IX gene, in which it is caused by deletions or substitution.

Figure 1: How Hemophilia Works
http://www.hemophilia.ca/en/bleeding-disorders/hemophilia-a-and-b/the-clotting-problem-in-hemophilia/

Gene Therapy

Introduction to the General Topic: Application of Gene Therapy

In brief describe about this application (what is it all about?)

Gene Therapy is the technique of inserting healthy genes into the human body to cure any disease, including genetic diseases, as to cure the mutated gene that is causing problems for the patient. In other words, genes are utilized as medicine. It is aimed towards being a potential treatment to cure genetic diseases such as cystic fibrosis, hemophilia and cancer. 

What are some benefits of this application?   

Gene Therapy allows people to be cured from a variety of diseases, in which they include genetic diseases and cancer. According to learn.genetics.utah.edu, successfully cured diseases through the use of gene therapy include immune deficiencies, hereditary blindness, hemophilia, blood disease, fat metabolism disorder, cancer and parkinson's disease.

What are some future improvements which still need to be done to make this application perfect (limitations)?

As said above, gene therapy is currently still being researched and experimented on to ensure its safety and effectiveness. According to betterhealth.vic.gov.au, between 1989 and 2010, 1698 clinical gene therapy trials were conducted. However it resulted to only less than 1% trials being a success and showed effective results with clinical benefits. Researchers are still studying on how to correctly deliver and activate the cell, how to avoid immune response that could harm the body and how to avoid disrupting important genes in target cells.

     What issues (social, economic, ethical, political or cultural) are currently related to the use of this application worldwide?

Gene Therapy has various ethical and moral issues. People tend to believe when gene therapy becomes known, researchers may start to have the same aim as genetic engineering through the use of gene therapy. People fear that normal and common characteristics of people will be considered as 'subnormal' and more discrimination among society will occur. Furthermore, another issue is concerned with money. This extremely common issue explains that gene therapy might be labelled with quite an expensive price, thus the poor is unable to afford the procedure and only the rich is capable of getting the treatment. 

Bibliography:

-  "Gene Therapy - Better Health Channel." Better Health Channel. N.p., n.d. Web. 06 Oct. 2014. <http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Gene_therapy>.

      - "Gene Therapy: Revolutionizing Medicine." Gene Therapy. N.p., n.d. Web. 06 Oct. 2014. <http://www.ndsu.edu/pubweb/~mcclean/plsc431/students/brandi.htm>.

      - "Gene Therapy Successes." Gene Therapy Successes. N.p., n.d. Web. 06 Oct. 2014. <http://learn.genetics.utah.edu/content/genetherapy/gtsuccess/>.

      - "Gene Therapy." Gene Therapy. N.p., n.d. Web. 07 Oct. 2014. <http://www.ama-assn.org/ama/pub/physician-resources/medical-science/genetics-molecular-medicine/current-topics/gene-therapy.page>.

      -  "Challenges in Gene Therapy?" Challenges in Gene Therapy? N.p., n.d. Web. 07 Oct. 2014. <http://learn.genetics.utah.edu/content/genetherapy/gtchallenges/>.

      - ScienceDaily. ScienceDaily, n.d. Web. 07 Oct. 2014. <http://www.sciencedaily.com/articles/g/gene_therapy.htm%27>.

      - "What Is Gene Therapy?" Genetics Home Reference. N.p., n.d. Web. 05 Oct. 2014. <http://ghr.nlm.nih.gov/handbook/therapy/genetherapy>.

      - "Gene Therapy." Gene Therapy. N.p., n.d. Web. 07 Oct. 2014. <http://www.ama-assn.org/ama/pub/physician-resources/medical-science/genetics-molecular-medicine/current-topics/gene-therapy.page>.