Welcome Agent 008

1. It is highly important that you complete this mission before Welcome Agent 008 Friday, October 12th, 2007 ends. It will require your skill & expertise I have a new mission for you

2. Are you in? Yes? See Agent 207 for a briefing Perfect.

3. biotech project might have information we need. You must be Agent 008 Here for your briefing, I suppose? It goes by the name "Gene Therapy" Well, we've caught word that a certain

4. Your job is to find the following What is this “Gene Therapy”? How does it work? What is its significance/benefits in society? How is technology used in this? What ethical issues might this involve? What are the potential problems of this? Good Luck. Remember your deadline

5. Ah-HAH! a clue

6. it says.. What is Gene Therapy? -a simple definitionby Karen Chen Gene therapy is a relatively new technique used to treat genetic disorders and diseases. The method is mainly used to correct defective genes that are responsible for the development of the disease. The most common practice of gene therapy is to replace a mutant allele* with a functional one. *for definition, visit http://dictionary.reference.com/browse/allele alright, time is ticking better find more info..

7. another clue! Ah-HAH!

8. Notes for Mission GT This tape appears to be a recording from some sort of Bio class on Gene Therapy. I’ve gotten my text gadget to record the words into a text version of it for quick reference. The clue was found at 10:46 AM, Thursday, October 11th, 2007. How Gene Therapy Works In the majority of studies on gene therapy, an ‘abnormal’ (disease-causing) gene is replaced by a ‘normal’ one by having the therapeutic gene inserted into the target cells of a patient. This is done by using carrier molecules called vectors to deliver the ‘normal’ gene to where it’s needed. Believe it or not, the most commonly used vector is a virus. Not any old virus though, these viruses have been genetically altered to carry normal human DNA. Nowadays, viruses have evolved a way of taking their own genes and delivering them to human cells to cause illness. Scientists have been able to use this to their advantage however by using this ability of theirs and manipulating the virus genome to remove the disease causing genes and insert remedial ones.If, for example, we wanted to replace abnormal cells in the liver, we would infect the patient’s liver cells with the viral vector. The vector will then dump its genetic material containing the normal human gene into the target cell. With the new therapeutic gene, the cell will generate functional protein which restores the cell to a normal, healthy state. Now, would everyone please have a look at this website: http://www.fda.gov/fdac/features/2000/gene.html

9. a clue was right beneath my nose! Ah-HAH!

10. October 11th, 2007 Toronto- It seems that everyday now a new biotechnology project comes in and you wish you had paid more attention in biology class. At a press conference concerning recent developments in gene therapy research, a brave man dared to ask, “How is gene therapy significant to us?” Dr. Peter Evans of the Gene Therapy Research Organization (GTRO) cleared his voice before answering, “Gene therapy is really an exciting topic. It can be used to do so much. Most commonly, we use it to treat genetic disorders like severe immunodeficiencies and so on. We’re expanding its uses all the time though, we have guinea pigs that were deaf with it, andwe recently had scientists prove that gene therapy can be used to effectively treat cancer.” “It can be used to do so much,” that quote sums it up pretty well. Upon further research, I saw the names of disorders and diseases treatable by gene therapy stacking up. Genetic disorders like X-SCID (severe combined immunodeficiency) or the "bubble boy" disease, sickle cell, myeloid blood diseases, even blindness were among a list of many others with results in varying success. Even Alzheimer's and weight loss made the list. For the future, gene therapy is looked at as a possible treatment for Parkinson’s and is already on its road to becoming an effective cure to some cancers. Ways of using gene therapy as a prevention technique against cancer and diabetes is also being looked into. If I were to bet my bottom dollar on how significant gene therapy is, I would; it’s just that significant.

11. Hmmm. Where could the next clue be? Actually, I am going to check my email, I deserve a break.

12. Now is when vectors come into play. The most common delivery method is to use a viral vector which is a virus that has been ‘deactivated’ (its own genes are removed) so that it is harmless. Since viruses can slip into cell and take over their DNA, scientists realised they could use this ability to enter a specific cell and deliver the healthy gene. There are several different types of viruses used as vectors in gene therapy. Retroviruses like Human immunodeficiency virus (HIV) can create double-stranded DNA copies of their RNA genomes. The copies of genomes from this class of virus can be integrated into the chromosomes of host cells. Other types of viruses used are Adenoviruses like the common-cold, Adeno-associated viruses and Herpes simplex viruses; each with its own advantages. I dug up some information on your behalf as Agent 000 told me to help out. There is a range of delivery techniques and several different types of vectors that can carry out the delivery of the healthy genes. First of all though, the affected cells need to be taken from the patient where the correct genetic information is then either ‘spliced’ or injected into the cells. Splicing used for gene therapy is when the incorrect gene is cut out from the DNA sequence and then modified to contain the correct genetic information. After it is modified, it is then inserted into a vector of some sort for delivery into the patient. Adeno-associated viruses can insert their genetic material at a specific site on chromosome 19. While Herpes simplex viruses infect neurons. As great as viruses are as vectors, there are many other methods of delivering the genes. Out of these, the simplest one would be to introduce the remedial genes directly into target cells but that would require large amounts of DNA and it can only be used on certain tissues. Another non-viral method would be to get therapeutic genes into the targets by chemically linking the DNA to a molecule that will bind to special cell receptors. When these are attached to the receptors, the therapeutic DNA structure is engulfed by the cell membrane and passed into the inside of the target cell. This method however, tends to be far less effective. To: 008 beachlover380@hotmail.com From: 307 skyhigh432@yahoo.com Subject: Technology and GT Gene Therapy itself is considered a technology but Agent 000 told me to give you some info about the specifics on the different kinds of vectors used for the process of gene therapy. I also found an outline of the steps in the process of gene therapy that I thought might be useful to you. I was searching through my old notes when I came across this outline of the basic steps in gene therapy and thought that I’d save you some trouble and send it to you. • Anyway, the outline consists of the following. • The faulty gene that is causing the disease must be identified. • You must locate the exact position of the affected cells • A healthy version of the gene must be available to replace the faulty one • Using some sort of vector, the healthy gene must be delivered to the cell. • Now, technology comes into play considerably during this process. And the information about them was extremely difficult to come across. However, Ah-HAH more info !

13. Is it more or less ethical to perform somatic gene therapy or germline therapy? Are disabilities diseases? Somatic gene therapy is performed on adults who are known to have the disease while germline therapy is done is egg and sperm cells to prevent a trait from being passed down from generation to generation. I personally think that germline therapy is perfectly acceptable. Idealistically speaking, if we prevented traits from being passed down, we could eventually get rid of a disease altogether. It also feels more safe knowing that you won’t inherit a disorder from your parents or that you won’t pass one on to your children. On the other hand, it is also unfair to determine something for others without letting them have the chance to make a decision for themselves. This would make somatic gene therapy more ‘fair’ since it is your personal decision but when we are born, we also have no hand in deciding what genes we want. Do they need to be cured or prevented? Some say: Yes, life is simply much easier without having to deal with a disability and no one should have to go through life like that. Others say: No, having a disability doesn’t make you any less human and you shouldn’t be regarded differently. Why should we try so hard to cure disabilities many people are living with today? It is practically demeaning their existence. Gene therapy is extremely costly to perform. Who will have access to these therapies? Who will pay for their use? Some say: Everyone and anyone should have access to these therapies. We are all entitled to equal rights and should be able to have the therapy we need performed no matter who we are and how much money we have. The government should pay for our fees, or at least subsidize them. If a treatment is available, anyone should be able to go have it done, no matter their financial situation. Others say: As much as we’d like to idealize and say that everyone should be able to have gene therapy performed, our society simply doesn’t work that way. It is extremely costly to have to procedure done and that kind of money is difficult to come by. There is almost no way that a patient could have it done for free without some serious changes like huge increases in funds or higher taxes in countries. A potential patient would have to be very financially secure for this treatment which unfortunately, at least for now, cannot be accessed by all. Ethical Issues

14. Short-lived results of gene therapy For gene therapy to be a permanent cure, many requirements must be met. First of all, the therapeutic DNA introduced into target cells must remain functional and secondly, the cells containing them must be stable and live for a long period. Long-term benefits can be prevented from success with all the problems integrating therapeutic DNA into the genome and the fact that some cells’ rapid dividing nature keeps gene therapy from ‘sticking’. As a result, patients often have to undergo several rounds of the treatment. Viral Vector Problems Viruses are usually the most common choice for vectors and viruses, although genetically altered, come with some risks. Such risks would include: toxicity, immune and inflammatory responses, and gene control and targeting issues for the patient. Finally, there is always the fear that once the virus has entered the patient, it may recover its ability to spread disease. Multigene Disorders Many of the most commonly occurring diseases like heart disease, high blood pressure, Alzheimer's disease, arthritis, and diabetes, are caused by the effects of variations in many different genes. The best candidates to receive gene therapy are disorders that arise from mutations in a single gene so treating diseases like those aforementioned would be difficult. Potential Problems Immune Response Our immune system is meant to attack foreign objects when they invade our bodies so there is always a risk of stimulating the immune system in a manner that would reduce the effectiveness of the treatment. And since gene therapy is often used on a patient several times, it becomes more difficult to perform since the immune system is especially good at responding to invaders it is familiar with.

15. better get back to headquarters now! Oh boy! Look at the time!

16. It was a project for my Bio II class. Congratulations. You were successful, I assume? You wanted to ask me something? Even top agents procrastinate. Of course you completed it. Oh. Well you see.. I see that you've made it 008.