Practical Considerations in Gene Therapy - Essay Example

Practical considerations in gene therapy I. Introduction Gene therapy is considered for situations where both life and quality of life are threatened (Cotrim and Baum 2008, p. 193). Earlier, the therapy has been considered only where life is at risk. About six years ago, in 2005, the United Kingdom Parliament Office for Science and Technology reported that “gene therapy is only used to treat very serious diseases” (p. 2). Yet, today gene therapy is considered for cases where risks, especially risks to life, are not even involved. Thus, gene therapy is no longer considered today as a treatment of the last resort. Therefore, there is a need to look into the practical considerations of gene therapy. The important practical considerations pertain to applications, problems, ethics, communications, and prospects. Using the perspective of Culver (1994a), Cotrim and Baum explained that gene therapy is a procedure that “typically involves the insertion of a functioning gene cells to correct dysfunction or to provide new cellular functions.” Culver (1994a) is a physician’s handbook on gene therapy. In 1994, Culver (1994b) had already outlined a procedure for the clinical applications of gene therapy for cancers. When a medical situation involves defective genes, an option to use gene therapy arises. Some of the diseases that result from defective genes include immunodeficiency syndromes, muscular dystrophy, cystic fibrosis, hemophilia, and many types of cancers (Cotrim and Baum 2008, p. 97). Another perspective on gene therapy comes from the United Kingdom Parliament Office on Science and Technology. According to the Office (2005, p. 1), gene therapy “involves the introduction of genetic material into a cell to treat disease.” Finally, another alternative definition of gene therapy is “transferring recombinant genetic material (DNA or RNA) to the host cell in order to change the gene expression in the host cell in order to change the gene expression in the host cell to attain therapeutic effect.” Most likely, the definitions we choose to adopt or highlight can be associated with the specific therapy or ailments on which we want gene therapy to work. II. History of gene therapy In was in the late 1960s that gene therapy was first considered as a possible therapy for humans (Evans and Robbins 1995, p. 1103). In those years, “the first target diseases were heritable, classic genetic disorders resulting from single mendelian genes made faulty by mutation” (Evans and Robbins 1995, p. 1103). At that time, “more than 4,000 such diseases have been identified, including cystic fibrosis, phenylketonuria, and beta-thalassemia” (Evans and Robbins 1995, p. 1103). The thinking in the late 1960s was that “transfer of the normal (wild-type) gene to a patient, followed by its appropriate expression, should compensate for the defect and treat the disease in many instances” (Evans and Robbins, p. 1103). In 1984, the topic “gene therapy” appeared in a publication of the United States Office of Technology Assessment and, at the time, the Office was still suggesting and seeking approval to use gene therapy for humans. The preface of the U.S. publication mentioned that gene therapy will “first be performed on patients who have no better prospect for treatment and who suffer from severe, rapidly fatal diseases caused by defective genes” (U.S. Office of Technology Assessment 1984). The 1990s saw the advance of clinical trials in gene therapy (Biceroglu and Memis 2005, p. 113). In 1995, doctors were talking about the possible applications of genetic therapy for orthopaedic patients. Evans and Robbins (1995, p. 1103) pointed out that “although originally intended as a means of compensating for heritable genetic diseases, gene therapy may also be used to treat acquired diseases with gene transfer used as a type of drug-delivery system” (Evans and Robbins 1995, p. 1103). Evans and Robbins (1995, p. 1103) clarified that “no clinical trials have yet been started for the treatment of diseases of the musculoskeletal system.” Evans and Robbins expressed that “it has been recognized that gene therapy need not be restricted to the treatment of classic genetic diseases” (p. 1103). Today, however, gene therapy has firmly established itself as a science even if it is “still at fairly primitive stage” (Cotrim and Baum 2008, p. 97). III. Gene therapy procedures Cotrim and Baum 2008 (p. 97) identified two general approaches for introducing genes into a cell. The first procedure is viral while the other procedure is nonviral. This is illustrated in Table 1. Table 1. General approaches in gene therapy Source: Cotrium and Baum (2008, p. 98) Citing a documentation in 2004, Cotrim and Baum (2008, p 97) pointed out that the viral approach is being used in around seventy percent of the cases. The viral procedure known as “transduction” is considered “extremely efficient” but the procedure has safety risks at the same time (Cotrim and Baum 2008, p. 97). Gene transfers through nonviral means are safer but have been inefficient in transferring genes (Cotrim and Baum 2008, p. 97). According to Cotrim and Baum (2008, p. 97), the common viral vectors used in clinical trials through transduction are usually from serotype 5 adenovirus (Ad5: ~26%) and Moloney murine leukaemia virus (MoMLV; ~28%). Transduction through the Ad5 vector is able “transducer both dividing and nondiving cells and facilitate highly efficient gene transfers (Cotrim and Baum 2008, p. 97). Most importantly, transduction through Ad5 vectors “only very rarely integrate into a chromosome (Cotrim and Baum 2008, p. 97). The main disadvantage, however, is that the Ad5 vectors induce a potent host-immune response (Cotrim and Baum 2008, p. 97). MoMOLV vectors target dividing cells and the procedure using the vector is valued because of its high efficiency and also because the procedure leads to “stable gene transfer because they integrate randomly into chromosomes of the target cell” (Cotrim and Baum 2008, p. 97). Unfortunately, the major risk of the procedure is the “risk of insertional mutagenesis caused by the integration of retroviral genome into the host genome” (Cotrim and Baum 2008, p. 98). Gene therapy through nonviral means also use two main approaches: direct injection of plasmids and the lipofection (Cotrim and Baum 2008, p. 98). Direct injection of plasmids has been used in ~14% of approved clinical trials (most often in muscles). Lipofection uses cationic lipids to surround the plasmid DNA (Cotrim and Baum 2008, p. 98). IV. Applications of gene therapy Recently, Cotrim and Baum (2008, p. 97) reported that some of the examples of the diverse clinical applications of gene therapy are in acquired issue damage, upper gastrointestinal tract infection, autoimmune disease, and systemic protein deficiency. Citing various studies and various works, Cotrium and Baum (2008, p.97) pointed out that gene therapy has been “especially successful” for treating combined immunodeficiency syndromes and demonstrated “lasting and remarkable therapeutic benefit.” Baker et al. 1997 reported that clinical trials were underway for the treatment of disorders as diverse as cancer, peripheral vascular disease, and monogenic diseases. In the following discussion, we discuss a few details on the use of gene therapy for specific conditions where gene therapy is believed to be useful or where gene therapy appears or appeared difficult to implement. 1. Gene therapy for acute inflammatory disease Moldawer et al. (1999) reported that transduction can be applied as a gene therapy for acute inflammatory disease and produced a schematic shown on Figure 1. Figure 1 represents the procedures involved in transduction. The team of Moldawer et al. (1999) has stressed that although non-viral gene therapy is attractive, the efficiency of using transduction methods must be improved in therapy involving acute inflammatory diseases. Figure 1. General schematics of transduction Source: Moldawer et al. (1999, p. 89) 2. Gene therapy for erectile dysfunction Figure 2. Gene therapy schematic for erectile dysfunction Source: Bivalacqua and Hellstrom (2001, p. 185) Another potential application of gene therapy is for treating erectile dysfunction. The basic procedure is outlined in Figure 2. As pointed out by Bivalacqua and Hellstrom (2001, p. 185), the diagram “demonstrate the administration of desire gene or cells into the corpus cavernosum and subsequent transportation into the nucleus and alteration of cellular function.” The said element is crucial in using gene therapy for erectile dysfunction. 3. Gene therapy for orthopaedic applications Kofron and Laurencin (2005) reported the state of the art in gene therapy for orthopaedic applications. According to Kofron and Laurencin (2005, p. 37), the mode of treatment for muscoloskeletal injuries often use cell transplantations, tissue graft, and artificial scaffoldings. They emphasized that the current modes of treatment may be augmented by the use of gene therapy to accelerate the generation of healthy tissues (Kofron and Laurencin (2005, p. 37). In particular, Kofron and Laurncin (2005, p. 37) reported that gene therapy can be achieved by the “direct transfer of the gene encoding the therapeutic agent to the cells of the afflicted tissue or by implanting cells that have been previously genetically modified in vitro” (Kofron and Laurencin 2005, p. 37). 4. Gene therapy in prevention of vein graft failure Baker et al. (1997) presented the possibility of using gene therapy for the prevention of vein graft failure. However, the authors also pointed out that the possibility for gene therapy on vein graft failure will be more distant because of the “highly complex, multifactorial aetiology of the disease.” Nevertheless, the authors identified some of the avenues the can advance the therapy in the specific condition. First, medical science in 1997 has acquired “the ability to selectively manipulate in vivo the expression of a specific gene within the graft wall, either by inhibition or by over expression” (Baker et al. 1997, p. 448). Second, the advances of medical science “to transfer therapeutic genes into the vein ex vivo prior to graft interpositioning provide a unique opportunity to alter the pathogenesis of vein graft failure” (Baker et al., 1997, p. 448). More than 10 years have past since Baker et al. (1997) and it is appropriate to check the advances in the use of gene therapy for prevention of vein graft failure. 5. Gene therapy in interventional radiology application Biceroglu and Memis (2005) reported the application of gene therapy in interventional radiology. Biceroglu and Memis (2005, p. 113) asserted that “since the vascular wall is a good target for this treatment, interventional radiologists should become familiar with this new therapy and be involved in this multidisciplinary collaboration.” The authors have a good narration on the mechanics of gene therapy in affecting proteins in the body, particularly on its paracrine or systemic effect and its importance for interventional radiology. V. Other Practical Considerations: Ethics, communications and prospects The specifics of gene therapy, including the procedures and modalities, are of course the most important practical consideration in gene therapy. Other than the said practical consideration, some of the other practical considerations pertain to communications, ethics, and prospects. For instance, in Australia, surveys indicate that there is a significant proportion in populations that questions the morality of technologies that alter genes although more than half of the population usually agree to gene altering technologies. On the other hand, Sphal and Deichmann highlighted the difficulty of communicating messages on biotechnology, including gene therapy. Based on these, concerns on the prospects of biotechnology were raised (Cotrium and Baum 2008). VI. Conclusion Thus, based on the discussion of this work, the practical considerations in genetic therapy covers modalities or choosing the efficient mode of gene therapy, addressing ethical issues, communications, and the prospects of the therapy given the practical considerations. References Agrifood Awareness Australia, 2009. Gene technology and ethics. Biotechnology Australia: Agrifood Awareness. Biceroglu, S. and Memis, A., 2005. Gene therapy: Applications in interventional radiology. Diagnostic Intervention Radiology, 11, 113-118. Bivalacqua, T. and Hellstrom, W., 2001. Potential application of gene therapy for the treatment of erectile dysfunction. Journal of Andrology, 22 (2), 183-190. Cotrim, A. and Baum, B., 2008. Gene therapy: Some history, applications, problems and prospects. Toxicologic Pathology, 36 , 97-103. Culver, K., 1994a. Gene therapy: A handbook for physicians. New York: Mary Ann Liebert, Inc. Culver, K., 1994b. Clinical applications of gene therapy for cancer. Clinical Chemistry, 40 (4), 510-512. Evans, C., and Robbins, P., 1995. Possible orthopaedic applications of gene therapy. Journal of Bone and Joint Surgery, 77 (7), 1103-1114. Kofron, M. and Laurencin, C., 2005. Orthopaedic applications of gene therapy. Current Gene Therapy, 5, 37-61. Moldawer, L., Edwards, P., Josephs, M., Minter, R., Copeland, E, and MacKay, S., 1999. Application of gene therapy to acute inflammatory diseases. Shock 12 (2), 83-101. Sphal, T. and Deichman, T., 2007. Communication of gene technology. Biotechnology Journal, 2, 1064-1066. U.K. Parliament Office, 2005. Gene therapy. Postnote 240. London: Parliament Office of Science and Technology. U.S. Office of Technology Assessment, 1984. Human therapy: A background paper. Washington: U.S. Office of Technology Assessment. Read More