Gene Therapy Essay Research Paper How does

Gene Therapy Essay, Research Paper

How does gene therapy work?

All life contains genetic information in the form of DNA. DNA can be reproduced and passed on to subsequent generations. A gene is a stretch of DNA that contains the blueprint for the sequence of amino acids making up a particular protein. Proteins are vital because they are used in catalyzing various biochemical reactions, they act as messengers, they regulate cell growth, development and reproduction, transport oxygen in the blood and are a defense against diseases. If a particular gene is mutated, its protein product may not be made at all, or it may work poorly or even too aggressively. This disrupts cell and tissue functions that depend on the normal gene product and causes abnormal cell behaviour, leading to symptons of disease. Correction of mutated genes can be carried out by introduction of a normal gene into the cell or by direct repair.

Gene therapy consists of three steps:

1) Administration: introduction of the gene or a vector containing the correct version of the mutated gene into the body

2) Delivery: transfer of the gene from the site of administration to the nucleus of the target cell

3) Expression: production of normal protein product in the cell, restoring normal cellular function

Somatic vs. germ-line gene therapy

Gene therapy is the deliberate transfer of DNA for therapeutic purposes. There are essentially two forms of gene therapy: somatic and germ-line gene therapy.

At present, gene therapy is being considered seriously only on somatic cells. Somatic gene therapy is the manipulation of genes in a patient’s cells. Any change will not be inherited in subsequent generations because target cells do not form a part of the germline.

On the other hand, germ-line therapy would involve genetic engineering that transcends generations. Gene therapy is targeted to germ cells. Any genetic modification of germ cells will be passed on to the next generation. This permanency frightens ethicists and it is largely due to ethical issues (as well as technical reasons) that little research is being conducted in germline intervention in larger animals and humans.

In vivo vs. ex vivo

There are two techniques for gene transfer: in vivo and ex vivo. Both methods employ vectors in order to deposit foreign genes into cells.

Ex vivo

Cells are genetically altered prior to implantation into tissues of the living body. This approach is generally applied in clinical trials because it is more efficient than in vivo methods. Scientists remove cells from tissue in the patient and expose them to gene-transfer vectors. The genetically corrected cells are then returned to the individual. One disadvantage to this approach is that reimplantation of altered cells grown in culture may not result in long-term survival. Genetically engineered cells grown in the laboratory need to be protected by encapsulation before injection. This approach is also limited to cells that are easily removed and replaced.

In vivo

Vectors containing the therapeutic gene are introduced directly into the human body. This can be accomplished by use of viral or non-viral vectors. An advantage of this method over ex vivo is that no specialized cell culture facility is required. However, there is low gene transfer efficiency because of poor access to target tissues and injected DNA is generally unstable.

In vivo gene delivery may be local systemic. In situ gene therapy is the direct introduction of genetic material into a localized area in the human body. Systemic delivery is still in development and relies on “smart” vectors that are injected and “home” to specific cell types anywhere in the body. With some form of targeting, the site of delivery becomes irrelevant as long as the therapeutic gene is released effectively and reaches its final destination.

The Achilles heel of gene therapy

Many of the fundamental problems of gene therapy have yet to be ironed out. Gene delivery and expression continue to pose a road block to the success of gene therapy as a therapeutically viable technology. Although the notion of gene therapy is scientifically sound, its application in clinical trials has not produced the hoped-for results. Obstacles in gene therapy include:

How to get the gene into a cell

It is not enough for the gene to be deposited into the cell. The chromosomes are housed inside the cell’s nucleus . The gene must be delivered to the nucleus in sufficient amounts in order to be therapeutically beneficial. Current methods for injecting foreign DNA are not generally not very efficient.

Gene stability

The therapeutic gene must become a permanent part of the host’s chromosomes so that it is replicated along with the patient’s chromosomes during cell division. DNA delivered by physical or chemical means can be placed in a cell’s nucleus and be expressed, but it will not be integrated into the host’s chromosomes. An ideal gene-delivery vehicle would be able to enter a large number of cells and integrate its DNA into the individual’s chromosomes. Some viruses are perfectly adapted to deliver DNA to cells. However, humans have an immune system that fights off the virus, inhibiting the success of the viral vector.

Activating the gene

The vector must contain a mechanism for activating the therapeutic gene. At specific times during a cell’s life cycle, certain levels of protein are required. Genes have evolved mechanisms that act as a “on” switch (promoter) to time and regulate gene expression. Promoters are often complex and large so placing the corrective gene’s own promoter into a therapeutic vector tends to pose a problem. Instead, promoters native to the virus are used. In some cases, these vectors worked quite well, but low levels of expression hindered the success of the therapeutic genes. Recent vectors include portions of the gene’s own promoters, increasing the level of expression and ensuring that the gene is expressed as naturally as possible – only during the times when it is needed. Other recent vectors pair a tetracylcine-sensitive promoter with a corrective gene. Certain genes have promoters sensitive to the antibiotic tetracycline and only when the patient ingests tetracycline is the gene activated.


One of the features that make viruses so attractive to gene therapy, that is, their ability to integrate genes into a host’s chromosomes also poses a serious drawback. Scientists have no control over how many copies of the genes become integrated or where on the chromosome they insert. This means that the vector may become inserted within another gene, disrupting or altering its expression. Or a gene may integrate within the regulatory region responsible for cellular proliferation and lead to cancer growth.


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