The Use of DNA as a Medicine - Essay Example

Gene Therapy Number Gene therapy can be defined as the use of DNA as a drug to treat disease by delivering therapeutic DNA into a patient’s cells/ it is a form of treatment involving the alteration of genes inside the somatic cells that halt disease/ an experimental technique that uses genes to treat or prevent diseases (Espejo, 2004). Commonly, gene therapy involves using DNA that encodes a functional therapeutic gene to replace a mutated gene. Other approaches of gene therapy include using in place of a natural human gene, DNA that encodes a therapeutic protein drug or directly correcting a mutation to elicit treatment. Gene therapy uses a vector which functions to deliver DNA inside body cells after packaging. The DNA, once in the body through the vector goes into the bloodstream then into cells and finally is incorporated into a chromosome. However, naked DNA approaches have been considered too more so in the field of vaccine development. Once embedded in the patient’s system, the DNA is expressed by the cell machinery, leading to the production of therapeutic protein which corrects the patient’s condition. Emphasis lies on administering a gene that will cause a protein to be expressed and that the patient specifically needs. In addition, with the advances in knowledge of nuclease functions in humans, there have begun explorations into ways of incorporating genes that encode nucleases into chromosomes. The expressed nucleases then disrupt the genes causing the disease by ‘editing’ the chromosome (Giacca, 2010). The concept of gene therapy was first thought possible in 1972 but caution was implored especially concerning its application/ experimentation on humans. In 1990, however, Ashanti DeSilva became the first recipient of gene therapy treatment in the United States for ADA-SCID. Early skepticisms arose with several initial clinical failures with many regarding gene therapy as an over-rated procedure but successes since 2006 have seen many regain their faith in this new form of treatment. Over 2,000 recorded clinical trials have so far been performed on humans. These include successful treatment of diseases such as multiple myeloma, Parkinson’s disease, Leber’s congenital amaurosis, adrenoleukodystrophy, hemophilia, ADA-SCID, chronic lymphocytic leukemia and acute lymphocytic leukemia. With such successes, many governments and companies (especially research institutions) have continued to invest even more on gene therapy. Recently, Glybera became the first gene therapy procedure to be embraced in Europe and the United States for clinical purposes after it was approved by the European Commission as treatment for disease caused by a defect in a single gene, lipoprotein lipase (Kelly, 2007). With focus heavily aimed at diseases which result from single-gene defects like hemophilia, sickle-cell anemia, cystic fibrosis, thalassemia, and muscular dystrophy, two main avenues have been widely pursued; disrupting genes that are not functioning properly (and causing the disease condition) and also adding a gene to replace that which is not working properly. Other methods such as developing drugs from nucleic acids such as antisense and small interfering RNA have been adopted too. However, this method is not strictly gene therapy as it does really alter chromosome but instead directly interacts with other bio-molecules like RNA to induce desired effects (Giacca, 2010). Basically, there exist two types of gene therapy (of which only one has been tested on humans). These are somatic gene therapy and germ-line gene therapy. Somatic gene therapy entails the transfer of genes into the somatic cell or body of an individual. In somatic gene therapy, the alterations and their effects fall only on the particular recipient patient. There is no transfer/ inheritance of such genetic modifications to the offspring and consequent generations. It therefore forms the core of most clinical trials (especially on humans/ volunteers) where a genome integrated or external episome/ plasmid is the therapeutic DNA transgene that treats disease in patients. Although somatic cell therapy is promising for treatment, a total correction of a genetic disorder or complete replacement of multiple genes in body cells is yet to be achieved. Most of the clinical trials are still in the early stages (Kelly, 2007). The other type of gene therapy, germ-line gene therapy involves modification of germ cells (sperm or eggs) by the introduction of functional genes which integrate into their genomes. This method on the other hand allows for heredity or passing of such changes into consequent generations. The germ cells fuse to form a zygote which develops into other body cells of the new organism. Therefore, of the germ cell is genetically altered, then all the cells in the resulting organism contain the altered gene. It is predicted to be a highly effective method of counteracting genetic disorders and hereditary diseases in future (Espejo, 2004). As earlier stated, gene therapy employs the delivery of DNA into target cells. This can be accomplished in two major ways – using naked DNA or DNA complexes (non-viral methods) and using recombinant viruses (biological nanoparasites/ viral vectors). As is common biological knowledge, viruses once inside the host take over the host cell biochemical processes and introduce their genetic material into the host in their replication cycle. This characteristic of viruses has been vital in gene therapy with viruses often used as an efficient means of delivering therapeutic DNA into patients’ cells (as a vehicle) after first removing the viral DNA and replacing with the desired DNA. Several viruses such as retroviruses, adeno-associated viruses, herpes simplex virus, adenovirus, lentivirus, pox virus and vaccinia have been successfully used as vectors during gene therapy hence (Giacca, 2010). However, trials reveal certain advantages of using non-viral methods over viral methods. Non-viral methods are suitable for large-scale production and low host immunogenicity. In the past, non-viral methods were less palatable because of their relatively low levels of transfection and gene expression but recent advances in vector technology have resulted into molecules and techniques that match the transfection efficiencies of viral vectors. Currently, there exist several methods of non-viral gene therapy such as magnetofection, the gene gun, infection of naked DNA, sonoporation, electroporation, and the use of oligonucleotides, lipoplexes, dendrimers and inorganic nanoparticles (Naff, 2005). In summary therefore, gene therapy basically involves replacing mutated genes that cause disease with healthy copies of the genes, inactivating/ knocking out mutated genes that are functioning improperly and introducing a new gene into the body to help fight the disease. Gene therapy holds a lot of promise of treating a wide range of diseases like cancer, cystic fibrosis, heart disease, diabetes, haemophilus, HIV, schizophrenia, usher syndrome, male infertility, Rubinstein-taybi syndrome, cataracts, maternal acute fatty liver of pregnancy and partial epilepsy – diseases that have remained enigmas in the world of science, have resulted in the deaths and despair of billions and have so severely ravaged mankind over time (Espejo, 2004). The scientific community, in addition, is abuzz with the prospect of wiping out certain genetic disorders entirely from the human gene pool. Gene therapy has an incredible therapeutic potential. By targeting the reproductive cells, genetic disorders and related ailments can finally be gotten rid of completely if the prospect is embraced (Naff, 2005). However, there are also several barriers/ problems/ challenges and risks pertaining gene therapy. First of all, all its effects can be short-lived with problems of integrating therapeutic DNA into the genome and rapidly dividing nature of many cells preventing gene therapy from achieving any long-term benefits. Patients have to undergo multiple rounds of gene therapy hence, and with the high costs associated with the procedure, it could be quite draining to say the least. There is also the problem of the body’s immune response. The immune system is stimulated to attack any foreign object and this tendency reduces the chances/ effectiveness of gene therapy. In addition, repeated gene therapies that would be needed would be rendered inconsequential because of the immune system’s naturally heightened response to ‘intruders’ it has previously encountered (Kelly, 2007). In addition to toxicity, immune and inflammatory responses regarding viral vectors, there is also the chance that once inside the host, a virus may revert to virulent forms and cause additional ailments. There is also the threat of developing tumors due to DNA possible integration into the wrong site, say in a tumor suppressor gene like p53. This fear has so far materialized in a number of clinical trials for example in the X-linked severe combined immunodeficiency (X-SCID) patients where hematopoietic stem cells were transduced with a corrective transgene using a retrovirus which caused T-cell leukemia in certain patients. Many have suggested however that this could be checked by adding a functional tumor suppressor onto the DNA to be integrated but this too is no walk in the park as the larger the DNA is, the harder it is to integrate into target sites (Giacca, 2010). As you can also scientifically deduce from our prior discussions, gene therapy is not particularly suited for multi-gene disorders. Single-gene induced ailments are its best specialty. Unfortunately, some of the most commonly occurring diseases such as arthritis, high blood pressure, diabetes, heart disease, and Alzheimer’s are a result of combined effects of variations of many genes. Multi-gene/ multi-factorial diseases such as these and others are therefore difficult to tackle using gene therapy (Kelly, 2007). Some sectors of the society, especially religion, in addition, have declared the concept of gene therapy blasphemous and sacrilegious. For them, this tinkering with the original genetic make-up of a man is equal to playing God. The potential of reproductive gene therapy also, would mean the creation of an undesired superior race (enhancement/ modification of human capabilities). It is like questioning God’s will and attempting to alter the way of nature (Espejo, 2004). For these and many other reasons therefore, I agree that gene therapy is not worth pursuing. The potential devastations and moral standing far outweigh its perceived merits. It is a poisoned chalice and a bomb waiting to go off. For one, the fact that it is expensive means it will be exclusively for the economically well-off (Naff, 2005). And in as much as many still naively want to claim that this technology will only be used for medicinal purposes, the fact of the current affairs of the world has it that some malicious nations will inevitably at one time employ such advances for military gains. Even nuclear power was initially an idea aimed at creating an extra energy source to light up homes and run machines – how noble. Yet look at where it has gotten us. If gene therapy manages to eradicate disease (a big IF – the procedure itself is not foolproof as we have seen) then it would inadvertently cause other deaths through such as warfare (a man is still a man, sick or not, most reeking ambition and hatred). The induced reduced immunities associated with the procedure would equally mean susceptibility to other fatal diseases (Naff, 2005) (talk of from a frying pan into a fire – literally). What can we learn from such debates except that the human race has always had a knack of missing the point and recycling mistakes? One can live a healthy lifestyle with or without gene therapy (for example, we are aware of how to and how not to contact HIV, how to live in order to keep the threats of cancer, diabetes and so on at bay and etc.) But I cannot guarantee what degrees of recklessness (individually and through world governments) will ensue with further advances in gene therapy. References Espejo, R. (2004). Gene therapy. San Diego: Greenhaven Press. Giacca, M. (2010). Gene therapy. Dordrecht: Springer. Kelly, E. B. (2007). Gene therapy. Westport, Conn.: Greenwood Press. Naff, C. F. (2005). Gene therapy. Detroit: Thomson/Gale ;. Read More