SOMATIC GENE THERAPY: Somatic gene therapy is the transfer of genes into the somatic cells of

the patient, such as cells of the bone marrow, and hence the new DNA does not enter the eggs or
sperm. The genes transferred are usually normal alleles that could correct the mutant or disease
alleles of the recipient. The technique of somatic gene therapy involves inserting a normal gene into
the appropriate cells of an individual affected with a genetic disease, thereby permanently correcting
the disorder (Neuman et al., 1982). The targeted cells may be bone marrow cells, which are easily
isolated and re-implanted. Bone marrow cells continue to divide for a person's whole life to produce
blood cells, so this approach is useful only if the gene you want to deliver has a biological role in the
blood. Delivery of a gene that has a biological role in the lungs, muscle, or liver would have to occur
within those targeted organs. In many cases, accessing the appropriate tissue or, if the gene is required
in multiple tissues (e.g., muscles throughout the body) ensuring it can be delivered where it is needed,
is a major problem (Sakaguchi et al,.2008).
Somatic cell is non reproductive. Somatic cell therapy is viewed as a more conservative, safer
approach because it affect only the targeted cells in the patient, and is not passed on to future generations. In
other words, the therapeutic effect of gene therapy ends with the individual who receives the therapy.
However, this type of therapy presents unique problems of itsown. Often the effects of somatic cell therapy
are shortlived. From the fact that living cell of most tissue ultimately die and are replaced by new cells,
repeated treatments over the course of the individual's life span are required to maintain the therapeutic
effect (Pathak et al,.2009). Transporting the gene to the target cells or tissue is also problematic. Regardless
of these difficulties, somatic cell gene therapy is appropriate and acceptable for many disorders, including
cystic fibrosis, muscular dystrophy cancer, and certain infectious diseases. Clinicians can even perform this
therapy invitro, potentially correcting or treating a life-threatening disorder that may significantly impair a
baby's health or development if not treated before birth. Somatic gene therapy is restricted to the actual
patient and is not passed on to his or her children (Cole strauss et al,.1999). All gene therapy to date on
humans has been directed at somatic cells, whereas germ line engineering in humans remains controversial
and prohibited in for instance the European Union. Somatic gene therapy can be split into two broad

categories:

1. EX VIVO: Which means exterior (where cells are modified outside the body and then

transplanted back in again). In some gene therapy clinical trials, cells from the patient’s blood or bone
marrow are removed and grown in the laboratory. Cells is exposed to the virus that is carrying the
desired gene. The virus enters gene into the cell’s DNA. The virus enters the cells and insert the
desired gene into the cells DNA. The cell grows in the laboratory and are then returned to the
patient by injection into a vein. This type of gene therapy is called ex vivo (figure 3) because the
cells are treated outside the organism (cheng et al,.1994).
.
IN VIVO: Which means interior (where gene are changed in cells still in the body). This form of
gene therapy is called in vivo (figure 4), because the gene is transferred to the cells inside the patient
body.
Viral vectors that are used in somatic gene therapy experiment included: retroviruses, adenoviruses,
adenoassociated viruses, and herpes simplex viruses.
RETROVIRUSES: Retroviruses were the first viruses used as vectors in gene therapy experiments. They
are unusual because instead of using DNA to carry their genetic information to the cell’s protein-making
machinery, retroviruses use a related material called ribonucleic acid (RNA) as their primary carrier of
genetic information. When retroviruses invade a cell, they use an enzyme called reverse transcriptase to
make a DNA copy of their genes. Other enzymes then incorporate this DNA copy into the infected cell's
DNA (Cheng et al., 1994). Although retroviruses have been used in most gene therapy experiments so far,
they still present many problems. Retroviruses can invade only cells that are actively dividing, limiting
potential targets for therapy to blood cells, skin cells, stem cells, and other fast-growing tissues. In addition,
the viruses have no specific targets in the infected cells' chromosomes. As a result, the genes they carry are
inserted in a haphazard manner (Caplen et al., 1995). Ideally, retroviruses insert genes into the middle of a
strand of DNA that does not contain other genes. The genes might, however, be inserted smack in the middle
of a crucial gene, rendering it defective and blocking key cellular functions, causing more damage than
repair. Retroviruses could also integrate new genes into a stretch of DNA where they could cause cancer.
Despite the presence of promoters, moreover, the added genes typically do not produce enough proteins to
effectively treat disease. In addition, the patient’s body generally recognizes retroviruses as foreign invaders,
provoking adverse immune responses (Djikmans et al., 2004). As researchers have grown more confident,
however, they have begun injecting altered retroviruses directly into tissues where the corrected genes are
needed and have, so far, observed few problems. In clinical trials of patients with cystic fibrosis, a disease in
which a mutated gene impairs lung function, healthy genes are inserted directly into the lining of bronchial
tubes (Kato et al., 2005). In studies of animals, researchers have used retroviruses to inject genes directly
into muscle tissue to learn if the genes will produce normal muscle proteins. Researchers hope this treatment
will one day help people with muscular dystrophy (Lehrman, 1999).

ADENOVIRUSES: To avoid the problem of inserting genes at the wrong sites, some researchers have

turned to other types of viruses, such as the adenoviruses, which cause the common cold. Stripped of their
disease-causing genes, adenoviruses take healthy genes into the nucleus of cells, where the DNA is located,
but do not usually integrate them into a cell's DNA. Researchers thus trade safety for impermanence,
because the genes persist in the cell’s DNA only for days to weeks (Mayeux, 2005). Adenoviruses can also
infect a broader variety of cells than retroviruses do, including cells that divide more slowly, such as lung
cells. However, adenoviruses are also more likely to be attacked by the patient's immune system, and the
high levels of virus required for treatment often provoke an undesirable inflammatory response. Despite
these drawbacks, adenoviruses have been used in attempts to treat cancers of the liver and ovaries (Kato et
al., 2005).
ADENO ASSOCIATED VIRUS: One of the most promising potential gene-delivery systems, or
vectors, is a recently discovered virus called the adeno-associated virus, which infects a broad range
of cells, including both dividing and non-dividing cells. Researchers believe that most humans carry
adenoassociated viruses, which do not cause disease and do not provoke an immune response.
Scientists have demonstrated that the adeno associated virus can be used to correct genetic defects in
animals. It is now being used in preliminary studies to treat hemophilia, a hereditary blood disease, in
humans (Robrish, 1999). The chief drawback of the adeno associated virus is that it is small, carrying
only two genes in its natural state. Its payload is therefore relatively limited. It can produce
unintended genetic damage because the adenoassociated virus inserts its genes directly into the host
cell's DNA. Researchers have also had difficulties manufacturing large quantities of the altered virus.
 HERPES SIMPLEX VIRUS: Scientists have found that the herpes simplex virus, the cause of the
common cold sore, has a very large genome compared to other virus vectors. This large genome
enables scientists to insert more than one therapeutic gene into a single virus, paving the way for the
treatment of disorders caused by more than one gene defect. The virus makes an ideal vector because
it can infect a wide variety of tissues, including muscle, tumor, liver, pancreas, nerve, and lung cells
(Sails, 2004). One problem with using herpes simplex virus is that the virus is cytopathic that is, it
kills the cells that it infects. In addition, the virus can cause encephalitis (inflammation of the brain) if
it replicates freely in the brain. Scientists are developing a form of herpes simplex virus in which the
genes that direct the virus replication and cell-killing abilities have been removed (Saiki et al.,
1985).