Gene Replacement Therapy

With our current society rapidly advancing in both the technological and medicinal world, many new treatments have been born that can be used to treat genetic conditions that regular antibiotics and surgeries simply have no positive or progressive effect. Gene therapy is when a newly developed gene is transferred, or introduced, to an already existing gene, it is the attempt to treat one’s genetic disorder at the molecular level and could significantly improve the human population and provides hope to people with disabilities. Gene therapy goes straight to the source and alleviates symptoms of the disorder. The gene receiving this new development is in some shape or form, mutated, or defective. If the gene therapy is a

The understanding of hemophilia has drastically improved over the last century. This has led to an improvement in the treatment of the disease. Despite this however, there has been little research in understanding how to prevent the transmission of the disease. The current understanding of the transmission of hemophilia greatly lags in comparison to the research poured into developing methods of gene therapy treatment.

Hemophilia A and B are x-linked disorders that cause bleeding due to the absence of a coagulation factor, which arise from mutations in the VIII (FVIII) and IX (FIX) factor genes1. Recent advances in the field of gene therapy have unveiled the use of adeno-associated vectors (AAV) and adenovirus vectors (Ad) to increase the levels of expression of the VIII and IX factors, counteracting the effects of the mutation 1. Gene transfer methods of the coagulation factor IX using AAV has resulted in dogs that had either sustained expression of the factor or that were completely cured from it 2. Gene therapy using Ad has a potential to treat Hemophilia B in the neonatal stages, but the possible leaky expression of this can lead to reduced efficiency of the vector 3. These two methods have the potential to treat Hemophilia by gene transfer.

There are two types of gene therapy: somatic gene therapy (SGT) and germline gene therapy (GGT). SGT involves treating a single individual by transferring therapeutic genes into somatic cells, most commonly bone marrow. GGT inserts genes into reproductive cells or embryos to fix genetic defects in the germ line. In other words, the genetic makeup of future generations is changed to prevent the recurrence of certain genetic disorders. Although gene therapy as a whole is controversial, germline gene therapy especially raises ethical concerns because it is capable of manipulating the human genome of a germ line. First, the risk is without the consent of future generations, and second, it may dangerously lead to genetic enhancement. Genetic enhancement has its own set of ethical issues, ranging from eugenics and social discrimination to messing with nature. Therefore, the potential consequences of gene therapy have raised a hotly contested bioethical question of whether gene therapy should be allowed in the future.

Since 1990, gene therapy had been tested in human clinical trials for treating such diseases as severe combined immunodeficiency disease (SCID), cystic fibrosis, Canavan's disease, and Gaucher's disease. ("Gene Therapy," n.d.). In the United States, gene therapy is only available in a research setting.

We carry about a thousand genes in us. Most of the genes we inherit come from our parents. Hundreds of genes can contribute to common conditions like breast cancer, Alzheimer’s disease, colon cancer, and rare disorders like cystic fibrosis and muscular dystrophy (Harvard Women’s Health Watch, 1998). Gene therapy is known to treat genetic diseases and other health problems. Figure 1 illustrates how gene therapy works. Genes are introduced into a human’s body by replacing the bad cell with a new cell. In Katherine Hunt’s article, (Gene Therapy), it explains the history of gene therapy that took place between 1970’s through 1990’s. In the 1970’s, scientists came up with “gene surgery,” to treat inherit diseases that are caused by bad genes. In

In a study titled “AAV-mediated factor IX gene transfer to skeletal muscle in patients with severe hemophilia B,” 8 patients were enrolled to further investigate the safety of intramuscular injection of adeno-associated viral vector. The study was also analyzed to determine the effectiveness and duration of F.IX levels. Seven of the 8 patients were also previously infected with Hepatitis C. Hence, muscle-directed gene therapy reduced the potential of certain complications compared to liver-directed gene therapy.

Gene therapy pro-actively transfers new genes into a patient therefore treating or preventing the disease. Gene therapy protocols follow two paths. Somatic gene therapy is a process in which hybrid retro vector is inserted into the cell. The vector binds to the cell membrane, packages itself in the vesicle which breaks down releasing it into the nucleus. Retroviruses are vectors harnessed for this task because their RNA genetic information can easily be transcribed into DNA. Furthermore, retroviruses introduce enzymes like integrase into the cell. Integrase incorporates new genes into the genome of a host. However, integrase can insert the modified genetic material in any arbitrary position in the genome of the host leading to insertional mutagenesis, and possibly cancer (Gene Therapy Retrovirus). Alternatively, cloned DNA solution is physically injected into a solution of zygote pronuclei during germline gene therapy In this way, the zygote produced has modified DNA which is passed to future generations. Nevertheless, germline therapy has a low rate of transgene integration in which modified genes do not get incorporated into the genome of the zygotes (Smith Kevin

In the last two decades, gene therapy has improved from mental concepts to clinical trials and laboratory experiment. Gene therapy is a technique that is currently being tested to see if genes can be used to treat or prevent disease. This method can successfully be able to replace a mutated gene with a healthy copy, knock out a mutated gene that is not functioning and introduce a new type of gene in the body to help fight a disease a human being may have. Gene therapy is a work in progress system that basically inserts a “normal” genome to replace the gene that is “abnormal” and causes disease.

Human Gene Therapy was first written about in 1963 with the first clinical study using gene transfer being conducted in 1990. Human Gene Therapy is characterized by the insertion of a functioning gene into cells to fix a cellular dysfunction or to create new cell function (Culver 1994). There are many diseases that come from dysfunctional or defective genes. These diseases include cystic fibrosis, combined immunodeficiency syndromes, hemophilia, and many types of cancer. (Cotrim & Baum 2008). A gene can be distributed to a cell using a carrier known as a vector. The most common vectors used in gene therapy are viruses. The viruses

The process for curing hemophilia post-birth would be to use “stem cells taken from people with hemophilia . . . [that] could be edited outside of the body to correct the genetic flaw that causes the disease, and then the normal cells [that] could be inserted to repopulate a patient 's bloodstream” (Specter 6). One example of genetic engineering being successful was when “In 1990, four-year old Ashanthi DeSilva, a child with SCIDS (Severe Combined Immune Deficiency Syndrome), became the first patient to be successfully treated using gene therapy as part of a clinical trial at the National Institutes of Health” (Specter 2).

Only somatic cells (body cells) are targeted. If the modified DNA is confined only to body cells then the genome that has been altered only effects the individual treated and not the offspring.

There are two types of gene therapy treatment: Somatic cell gene therapy and germline therapy. Somatic cell gene therapy involves obtaining blood cells from a person with a genetic disease and then introducing a normal gene into the

This could eliminate the need to have continuous treatments, as is most common today. While research still needs to be done to make sure there are no negative long term effects to this treatment, this study demonstrated the promising future for a new embryonic stage treatment for hemophilia A. It provides a direction for future research to follow regarding the use of embryonic stem cells to treat genetic diseases.

Abstract: Gene therapy is an experimental technique that uses genes to prevent or treat diseases. The process was initially designed to introduce genetic material into cells to compensate for abnormal genes or to make a beneficial protein. These abnormal genes, often caused by single nucleotide polymorphisms, can affect how humans develop diseases and how they will respond to pathogens, drugs, and other agents. Although gene therapy is a promising treatment option for a number of diseases and disorders, the technique remains risky and is still under study; it is currently only being tested for the treatment of diseases that have no other cures.