10/07/2016
Gene Therapy: What is it?
07
Wednesday
Oct 2015
Posted by Mina Viatcheva in Gene Therapy ≈
TagsAlzheimer's disease, cancer, Cystic Fibrosis, gene therapy, HIV, non-viral verctors, treatment, viral vectors
Gene therapy is an innovative technique, which aims to help cure or at least correct inherited disease, treat cancers and introduce genetic material in order to generate immune response in some way to provoke the bodily system to fight. This methodology idea became rather promising at the beginning of 1990s, since many conventional treatments are unable to achieve the desired results. The European Commission gave the first license for the employment of this approach only in 2012.
Nowadays, gene therapy is used manly to treat cancer patients in the most progressive stage of the disease, as the trials are still considered experimental and many countries do not grant the technique the trust as in the more conventional approaches (such as chemotherapy and medication). One of the great positives in employing this method is that there are no side effects as with other treatments.
Gene therapy can be ex vivo or in vivo, systematic or local. In the ex vivo approach, the desired type of cell is taken from the patient, grown in a petri dish in the lab, treated with the vector carrying the correct genetic information, and then re-introduced into the patient. This method is harder, requires very controlled and sophisticated protocols and safety. HIV and Alzheimer’s disease have been trialed for ex vivo gene therapy. The in vivo methodology delivers the vector carrying the chosen genetic material right into the target cell, meaning it is done directly into the patient. This process is less invasive, requires less controls and protocols, but it cannot be tested for safety, and at times it is hard to target precisely the selected cell. The in vivo gene therapy has been used to treat the majority of cancers and Cystic Fibrosis. The delivery of the gene products can be carried directly to the site of treatment, hence locally, and is used to treat rheumatoid arthritis. Systematic delivery, however, involves the application of the treatment to more than one site, most often done via the circulatory system. This technique is used to treat lung cancer.
The treatment needs to target different cell types according to the process in which the disorder develops and can be treated. Once delivered, the new gene product can switch off a faulty gene for a correct one (done for genetically inherited disorders); it can also illicit an immune response that will allow the T-killer cells to destroy a damaged cell (done for tumors); or it can induce proteins production that will involve the healing of cells (done for broken bones). Overall, the opportunities to implement gene therapy appear to be endless, and since most genetic information involved in particular disease is still undergoing research, we are just scratching the surface in what could be one of the most promising and sophisticated methods for curing disease.
Burette in flame/steam. Concept of medical research etc.
One of the biggest problems in this theoretically perfect solution arises from the delivery method used. Not only does the newly introduced genetic material has to be at the perfect place (meaning, in the precise cells we target), but it also has to be taken up into the cell and expressed properly. This has been done using vector deliveries, which can be classified as viral and non-viral.
Viruses have developed an efficient way to integrate their genetic material into the host cells, which makes them potentially powerful tool for vectoring DNA into a patient cell. Viruses are usually pathogenic, however, in this case, the DNA coding for the disease (coding for host cell damage and replication) is removed and replaced by the corrected gene one wants to introduce. Only the systems of delivery, integration, and expression are kept for the treatment purposes. Some of the most used virus vectors come from retrovirus (HIV), lentivirus, adeno-assiciated virus, and herpes simplex virus (herpes). All the vector systems used have advantages and disadvantages, and are suited for particular types of disease. Unfortunately, this technique still involves risks such as mutations or deletions of important genes (such as oncogene, involved in developing of cancer). Self-disabling viruses are used to control for this possibility, nevertheless, the risks associated with the treatment still remain.
On the other hand, we have non-viral vectors that have been developed with the idea to overcome the problems arising from the use of viral vectors. Nevertheless, besides being able to introduce the vector into the host repeatedly and risk-free, while inducing relatively low immune response; this approach has problems with the delivery and expression of the genetic material into the patient. Moreover, when this difficulty is surmounted, the problem of the method being only local still lingers. As one can anticipate, for centuries, viruses have been developing and evolving mechanisms to infect and propagate their genes into the host. Non-viral organisms do not exist, and therefore, we have to cultivate all this evolutionary mechanism in the lab. There are biochemical vectors, which pack the genetic material needed to be delivered, into cationic (positively charged molecules) lipids (very often cholesterol), and then delivered into the patient. There the positive charges of the lipid will react with the anionic (negatively charges molecules) DNA, so that the delivery can be released. Biocompatible, biodegradable polymers are also used in a similar manner, and can be administrated by aerosol or intravenously.
Gene therapy has a rather promising future, however, the race between the disease that can be induced by the use of viral vectors and the researchers is still very strong. This approach being so new still runs high risk of harming patients, but it also possesses the capacity to become the nearest thing to genetic correction directly into the source (almost making us play Gods). Where vector delivery is not to be used, the biochemical vectors, polymers, and even nano particles can be employed. However, a lot more research and trials need to be done, in order to deem the technique safe and reliable.
The Controversy of Genetically Modified Organisms (part II)
04
Sunday
Oct 2015
Posted by Mina Viatcheva in GMOs ≈ Leave a comment
TagsAgricuture, biodiesel, biofuels, GEO, GMO, Golden rice, ma*****na
(continued)
An example of GMO for health reasons is the Golden rice. Rice usually does not produce much vitamin A, however, its genetic information carries the ability to produce it if further “modified”. Therefore, since it is a staple food for many developing countries, industries and governments saw the opportunity to expand and offer it as an alternative. It is developed in such a way that it produces pro-vitamin A (beta carotene) by the introduction of two new genes – psy and lcy. The first is coming from daffodil and is responsible for the photosynthetic sensitivity needed for the reaction to propagate. The later is taken from the soil bacterium Erwinia uredovora, and is concerned with the lycopene production, which is further turned into precursor for vitamin A, so that when it is in the bodily environment, the vitamin formation can occur. As a result, the Golden rice is 23 times more “potent” than the regular one. Nevertheless, even though it is an excellent idea, most countries in which it was introduced consider their rice “sacred” (if I may say). And since the variety of rice crops is so vast, and the tastes differ around the world, the Golden rice never had the chance to become the big thing it promised to be.
The newest hype in GMOs is the ma*****na plant as we are coming to see more and more health benefits from it. In order to produce cannabis that produces cannabinoids that are health favorable, as opposed to those that have more psychoactive ones, we need to genetically modify the plant. This has been done, but usually so that it boosts only the psychotropic properties. For example, in the ‘70s, ma*****na had only 1-5% of psychoactive THC, whereas, nowadays, it has risen up to 35%. Nevertheless, this might not be the most desirable effect one is looking for when producing oil extract strictly for medicinal purposes. Therefore, altering the genes already present in the plant (one way or another) can result in a better alternative for people seeking cure as opposed to high.
Another great example for the application of GMOs is in the newly growing field of biofuels. In some cases, where bioethanol was to be derived as a desired biofuel, corn and palm have been used. However, the most favorable source of biodiesel turns out to be the lipids produced by alga (a multicellular microorganism capable of photosynthesis). Algae consume carbon dioxide, which in turn is converted to oxygen, water and lipids (the sustainable fuel for the survival of the organism). The variety of algae is rather vast, and in some species, half their weight is accounted by the produced lipids, we seek to make biodiesel from. The research in this field has its biggest facilities in the United States (subsided by the Army) and in Iran (subsided by the government). At a conference I attended, where one of the lead scientists in the lab in the United States spoke, he shared how they would use the specie, which will yield the highest amount of lipid in its reserves. Then, they will modify the genetic expression of the concerned gene to stimulate even higher production. Some of their attempts to produce “gold mine” specie also involved mixing two different, but compatible algae. As our fuel resources are depleted faster and the issue to find an alternative solution to satisfy our needs is pressing on us, GMOs seem to be well-fitted substitute.
Paprika in two colors with a syringe. Concept for GMO.
One of the main negatives surrounding GMOs, apart from the effects it might have on human health, are conservational concerns. Since plants pollinate in order to reproduce, the genetic modifications that had been introduced in one plant can be transferred into another. Not only that, but it has been speculated that these genetic alterations can leak into the soil, and subsequently into other species. This can be worrisome, for farmers who desire purely organic and untransformed crops. It is concerning also in ecological point of view where the selected traits of a plant that had been chosen (as said earlier, most often resistance to stressors) will overpower the naturally occurring one. This way, we can observe that weeds and insects that have evolved to be resilient to the induced changes become predominant. Subsequently, harsher and higher quantities of chemicals will need to be sprayed, new ways to exterminate unwanted pests and plants will need to be designed. Some species could disappear completely (such as bees) and as a whole, if not done thoughtfully, GMOs have the potential to shake severally the ecosystem. As widely known, pollinators not only help plants mating, but they also depend on the fine pollen for theirs and their offspring survival. If the plants are GE to ward off insects for example, then the harmless species will be affected too. They will stir away from the crops, ultimately running out of food to feed on, which could result in the inevitable loss of key species (the existence of which determines the survival of many more others). Most people do not see that as a potentially big problem; however, an increased introduction of GEOs has the very plausible chance to lead us to catastrophic times.
The Controversy of Genetically Modified Organisms (part I)
03
Saturday
Oct 2015
Posted by Mina Viatcheva in GMOs ≈ Leave a comment
TagsAgricuture, corn, GEO, GMO, Mendel
GMOs (genetically modified organisms), also known as genetically engineered (GE), are organisms whose genetic code has been altered through manipulation, so that its genotype (genetic material) and phenotype (physical appearance) differ from the expected majority. The genetic modification can be done by either changing the DNA in as such a way that its product is somewhat different from the naturally occurring, or by introducing a foreign gene taken from another specie.
The earliest genetic alteration ever known was grafting, where two different but somewhat compatible plants are made to produce a third, which would express some genes from one plant and others from the second (e.i. very often, pear and quince had been mixed together, to produce a hybrid which will be more edible than the quince, but stronger than the pear).
The main idea in genetically engineering an organism is to make it better fit to its environment, to gather higher produce, and at times for medical purposes.
The main and just objective is to make the GE species more durable, more resilient to stressors (infestations, environment), more efficient at producing a desired product, and to have higher product yield. As an idea, genetic engineering has good intentions, but as most great ideas on paper, when in the wrong hands, the idea can give birth to a monster. Some times, the idea cannot flourish due to cultural clashes, other times it is due to preservation issues. At times, it has been lost due to wrong approach, or might as well be just lack of knowledge and interest.
GMOs are surrounded by a lot of stigma and confusion, but so far they have not been scientifically proven to cause harm to humans. One of the reasons is that food industries sabotage such research, as these data might harm their profit. Another problem comes from the fact that human trials are lengthy and very often not empirically true (as there will be many more factors influencing the results from person to person; e.i., does the person smoke, is the person healthy overall, does the person exercise, etc.). Furthermore, many good ideas have been buried in the hands of huge companies, which subside university projects, and when a noble idea arises, they patent it and it is “gone”. There are many great opportunities to do good for humanity with GE organisms, but governments do not sponsor scientific projects as much as they should. Therefore, when something beneficial comes around, most people do not hear about it, left alone profit from it. And lastly, most experiments that have been conducted are biased, and at times, even tampered with, which makes the topic be seen as through a kaleidoscope.
gmo concept
In the world, the main genetically engineered crops that had been allowed and put in mass production are soy, corn, and cotton. For example, GE corn (which accounts for about 85% of total production in North America) is modified in such a way that a gene from Bacillus thuringensis (Bt), which produces a toxin harmful to insects, is integrated in the plant genome, so that infestations cannot affect severely the yield. The DNA has been also modified so that the corn can undergo harsh herbicide spraying without being affected. Many people will argue that integrating this “toxic” gene into the corn will inevitably harm us too. However, the human kind does not have the pathways, nor the enzymes required to get affected by this modification. As a whole, there are two points of view working overtime – “If bugs don’t want to eat it, then how could it be good for me?” and “Well, if chocolate is toxic for dogs (which it is), would you stop eating it?” – which one is true, only time will show.
For many years, people have been selecting for particular characteristics in plants by cross breeding and selection. The first “officially genetic” experiment was conducted by Gregor Mendel (1822-1884) in the 19th century. He noticed that green peas produce different flowering patterns, which also result in different phenotypes of the seed, pod, stems and peas. There were white and purple flowers, which produced green and white pods, with bigger or smaller beans in it. G. Mendel decided to cross breed the given varieties and observe the hybrids formed in a very meticulous and precise process. In short and simple words, he was the father of genetics, as he deemed that there must be some dominant and some recessive genes at role, hence he established the Laws of inheritance. Here I must say, those experiments did not produce any harmful products; we just implemented the law of natural selection pinned by Darwin, and then through careful selection certain traits were chosen and mixed to give birth to the Laws of Segregation and Independent Assortment. The same thing has been done by our ancestors for millions of years before us, by using the same procedure of cross breeding or by grafting. Was it wrong or was it right?
We can also add the example of our domestic animals. Technically speaking, the amount of breeds invented is also a result of genetic manipulations and selection of particular traits. In fact, the modifications are so vast at times that the hybrid animal does not even remotely resemble its parental specie. This being said, is it reasonable to doom all GMOs? Maybe, if they threaten the existence of their ancestors. But if they do not, then we should not speak in general terms for all genetically engineered organisms.
(to be continued)
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