Sunday, January 5, 2014

Gene Therapy

The Human Genome 
The thought of sequencing the entire genome began in the 1980s. At that time, the Sanger Sequencing Method was used, but it could only sequence a few genes. However, the possibility of sequencing the entire human genome was discussed by the U.S. Department of Energy between 1984 and 1986.  The Human Genome Organization was developed around the 1990s to coordinate genomic research internationally. Finally, the first part of the human genome was completed in 2001 and then in 2003 the entire genome was sequenced. It is important to have the entire genome sequenced because scientists will be able to determine the 3 billion base pairs that compose the DNA. This allows scientists to identify normal versus faulty genes.

What is Gene Therapy
Gene Therapy was first discovered in the middle of the 1970's. Researchers were able to isolate and cordon off certain genes from DNA. The definition is, "a technique where the genes causing a defect are themselves substituted by correct genes in the patient to cure a disease." Gene Therapy is an experimental approach to treat genetic mutations. A genetic mutation is a problem with a specific gene in the DNA. There are two types of genetic mutations, point mutations and frame-shift mutations. Usually genetic mutations cannot be fixed, but using gene therapy, there is a possibility that these genetic disease can be cured. Gene therapy cures these diseases by replacing the gene that is causing the problem.
Genes code for specific proteins that compose one's DNA sequence

The History of Gene Therapy
The first gene therapy trial was launched in 1991 and was planned to treat an immune system disorder called adenosine deaminase deficiency. Adenosine deaminase deficiency weakens the immune system and causes people with mild colds to have a hard time fighting off these infections. 

There were two patients who underwent this gene therapy trial. One of the patients had a moderate recovery while the other patient, a young girl named Ashanti de Silva recovered very rapidly and showed a huge improvement from this operation. This gene therapy trial with Ashanti de Silva showed that gene therapy is a cure for genetic diseases.

Several gene therapy trials were conducted throughout the 1990s. However, in 1998 a gene therapy trial was underwent at the University of Pennsylvania, but unfortunately it ended poorly and Jesse Gelsinger died from this treatment. After this incident, critics and scientists declared that gene therapy should no longer be called a therapy, but instead an experimental procedure.

Above is a picture of Jesse Gelsinger
The picture above is a picture of Ashanti De Silvia, the first person who underwent Gene Therapy
How does Gene Therapy Work
The first step of gene therapy is that the scientists have to find the problem gene. Once the problem gene is located, the scientists then insert a biological agent that delivers DNA called a vector. A vector gets inside the cells and inserts their genetic material into that cell's genome. The most common vector is a virus. Viral vectors are advantageous because they do a good job of coming into a cell and targeting them. In order for a virus to be used as vectors, the virus’ genes have to be taken out and replaced with the new gene that the mutated cell is lacking and requires. When the virus reaches the cell, it inserts its own genetic material and the new gene that the cell requires. However, viral vectors can not always be used and there is not a certain vector that can treat every disorder. Actually, one of the most difficult parts of gene therapy is that you have to find a suitable vector that will cure the disease.  Gene therapy is successful when the mutated cell now contains the new gene that will fix the problem caused by the faulty gene.

Gene Therapy using an adenovirus
In gene therapy different viruses can be used as vectors. The viral life cycle is reliant on the cell it is living in because the viruses cannot live on their own, and feed off of the cell. An example of a virus that is commonly used for ex-vivo gene therapy, which is also known as out-of-the-body-gene-therapy, is a retrovirus. The material in a retrovirus is made up of RNA molecules. The retrovirus goes through a reverse transcription and uses reverse transcriptase, which is a DNA polymerase that uses RNA as a template. The retrovirus is used because it is the only virus that is able to turn RNA into DNA and permanently change the genome.

There are several types of gene therapy. In-vivo gene therapy, also known as in-the-body-gene-therapy, includes good genes being put into a tumor. In ex-vivo gene therapy scientists draw blood or bone marrows from a person and split up the immature cells. Another type of gene therapy is cosmetic gene therapy. Skin color, eye color, hair color, baldness, height, and weight can also be changed and modified with gene therapy. Cosmetic gene therapy has been experimented with fish. Fish have been made into giant fish by giving the fish extra growth hormone, which stimulates bone and muscle growth.

How Gene Therapy Works

Future Prospects
Gene therapy has had more ups and downs than any biology technology. There have been several positive trials with gene therapy, but there have also been trials that did not go so well and have resulted in death. 

A recent trial of gene therapy was underwent to cure SCIDs. SCID is a combined severe immunodeficiency. This trial was led by Dr. Alain Fischer and it was thought to be successful until some of the patients developed leukemia. Some patients treated with this gene therapy developed leukemia because the vector placed itself close to a gene called LMO2, which is typically involved in leukemia.

The issues that Fischer faced have aided scientists in finding what needs to be fixed in order to make gene therapy safer and more effective. It was found that safer vehicles must be made, an action plan will need to be made to lower the immune rejection of the vector, and people need to acknowledge the risk of gene therapy. A safe vehicle is a vehicle that enters the mutated cells and then the vehicle puts itself into a safe place inside the genome. A safe place inside the genome is a place far away from any genes. Making safer vehicles and proposing an action plan to lower the immune rejection of the vector may take many years to resolve.

Gene therapy also has the potential to be able to fix diseases. There are many on- going trials to cure diseases like cystic fibrosis, parkinson's disease, cancer, and leukemia. In the future, there should be cures for all of these diseases since there have been some successful trials to treat this diseases. However, most of the gene therapy trials that are being experimented with today are aimed at curing several forms of cancer. Cancer is caused by changes in our genes. The cancer cells would be removed without actually being harmful to the normal tissues. Therefore using gene therapy for cancer can be a substitute when other treatments do not work. The future for gene therapy is huge considering it is one the keenest fields of medical research right now.

Pros and Cons

The Pros:

  • Gene therapy is is the only chance to being able to find a cure to genetic disorder that is otherwise incurable. 

  • If gene therapy is successful then it can cure the disease rather than just alleviating the symptoms.

  • There are thousands of genetic defects that could be treated with gene therapy.

    • If gene therapy picks out the reproductive cells it is probable to clear out the flawed gene, and may even be able to remove the whole disease entirely. 
    • It can wipe out genetic diseases before they actually occur and eliminate suffering and pain for future generations after.


    • Only a small percentage of genetic defects are considered candidates for this type of treatment. Diseases that can be cured by gene therapy are debilitating disorders.

    • It is very difficult to introduce new genes into the body

    • Sometimes adding the “good” copy of the gene doesn’t fix the issue. for example, if the mutated gene codes for a protein that doesn’t allow the normal gene to do its job, then adding the normal gene will not help or work.

    • There is little real knowledge and comprehension, so this means that the safety of gene therapy is uncertain.

    • The people who have gone through the gene therapy process and got effective results only lasted for a short amount of time
    • Can be dangerous and special attention must be given during the gene replacement operation
    • Genes could easily be delivered to the wrong cell and this could cause serious health problems for the patient
    • Since scientists still have little knowledge about gene therapy, the vector that is injected into the gene can easily be misplaced into the wrong gene, which can ultimately lead to even worse issues.

      Making Gene Therapy Successful

      1. Targeting the Right Cells
      2. Activating the Gene- The gene must go to cell’s nucleus and be activated, which means that its transcription and translation needs to work in order to make the protein that is put into code by the gene.
      3. Integrating the gene in the cells- The gene could possibly be needed to stay put and work on target cells. In order to do this, the gene needs to integrate, which means that it needs to become part of the host cell’s genetic material
      4. Avoiding harmful side effects- If there is an unknown substance injected into the body, there is a chance that the substance can be toxic to the body or the body will create a immune response against it. If the body has immunity against a gene delivery vehicle, then the treatments of therapy given will not work.

    Discovery Communications. "D News: How does Gene Therapy Work: Discovery." Discovery News. Last modified 2013. Accessed December 16, 2013.

    Gene Therapy. "Pros and Cons." G Last modified 2014. Accessed January 8, 2014.

    "Gene Therapy Breakthrough in Cancer Treatment." CBS News. Video file. Posted December 7, 2013. Accessed January 8, 2014.

    Gene Therapy Net. "Viral Vectors." Gene Therapy Net. Last modified 2013. Accessed January 8, 2014.

    Panno, Joseph. Gene Therapy: Treatments and Cures for Genetic Diseases. Rev. ed. New York, NY: Facts On File, 2011.

    Photography: 526524. Photograph. National Geographic Creative. 2014. Accessed January 8, 2014.

    Scientific American Inc. "How Does Gene Therapy Work." Scientific American. Last modified 2014. Accessed January 8, 2014.

    Stephenson, Frank Harold. DNA: How the Biotech Revolution Is Changing the Way We Fight Disease. Amherst, N.Y.: Prometheus Books, 2007.

    "Understanding: Gene Therapy Treatment." How Stuff Works. Video file. Posted 2014. Accessed January 8, 2014.

    U.S. National Library of Medicine. "What is Gene Therapy." Genetics Home Reference. Last modified December 10, 2013. Accessed December 16, 2013.


    1. Your blog is very interesting and has a lot of good information. I would just change the titles font size because they are a bit small and also are a different font than the actual text. Also, the last couple sections are a bit lengthy, so if it's possible I would try to shorten them just a bit. Overall great job!

    2. Your blog has a lot of interesting information, photos, and videos. Great job!

    3. I really liked how you guys organized your blog, the diagrams and videos also made gene therapy easier to understand.

    4. Besides a couple gramatical errors great job on the blog.

    5. I like the abundance of pictures in your blog. It makes it look appealing to the eye. The videos are also very interesting.

    6. I wouldn't have so much space between your bullet points, it makes it look like you are just trying to fill space.

    7. This is a great, well organized, blog. I like how you use many pictures, diagrams, and videos.

    8. Great job! One problem is that at the end you say the following treatments of therapy, yet there are no following treatments of therapy. Also I have a question about the cons. Are all benefits that ever happened on people this worked on temporary?

      1. No, the benefits were only temporary for some people, but it is considered a con because if gene therapy was completely successful then the benefits should never be temporary.

    9. I love the visual aids and specific situations you have in your blog!

    10. One suggestion I would make is to explain how this operation could be done safely. As you showed with your research about Jesse Gelsinger, he did not take to the therapy well. Is that an unfortunate chance or is there a way to make this therapy successful every time?

      1. It was an unfortunate chance and there is a lack of knowledge on gene therapy so thats why there are failures. Once scientists do more research and find about more about gene therapy, I'm sure there will be more successes.

    11. I liked the big pictures, diagrams and videos. It is so much more interesting to read than a huge paragraph.

    12. As I was reading the science behind gene therapy, some of the terms were a bit confusing at first. Maybe if you explain it slowly and in-depth it might not be so bad. Otherwise great job!

    13. I love the information and I thought the blog was done well. Also, the video was very helpful.

    14. When I was reading the "How does Gene Therapy work" section I got a little bit confused. I think that some of the terms should have been explained more.

    15. I really like the color scheme! It's really pretty and makes it more appealing to read.

    16. The blog is overall great, but I would suggest shortening or adjusting the section on how it works. I know there are already two, but maybe adding one or two more diagrams to the section could help people visually understand! Great job though!

    17. I honestly didn't really know anything about gene therapy before I read this, and I think your blog gave a really in depth and great explanation of what gene therapy is. Great Job!

    18. Some of the sections were a bit too long, so I would suggest shortening them a little.