Gene therapy

Gene therapy involves the delivery of therapeutic genes into the human body to correct disease
condition created by a faulty gene or genes. Providing a person with normal genes to supplement
defective genes and cure disease or even using normal genes to replace faulty genes.
How is it done ?
There two primary strategies for gene theraphy are in vivo and ex vivo. Technically speaking, introducing
DNA into animal or plant cell is transfection. For instance, liver cells from a patient suffering from a liver
disorder would be surgically removed and cultured. Appropriate therapeutic genes would then be
delivered into these cells using vectors and other approaches that we will discuss in the next section.
These genetically altered liver cells would then be transplanted back into the patient without fear of
rejection of the tissue transplant because these cells came from the patient initially. One challenge of in
vivo gene therapy is delivering genes only to intended tissues and not tissues throughout the body.
Scientiest have primarily relied on using viruses as vectors for gene delivery but in some cases genes
cases genes have been directly injected into some tissues. So far, ec vivo strategies have generally
proven to be more effective than in vivo approaches.
Delivering the payload : Vectors for gene delivery
A major challenge that must be overcome if gene therapy is to become reliable tool for treating disease
is achieving a safe an effective delivery of therapeutic genes the payload. Depending on genetic
condition to be treated, some therapeutic strategies may require long-term expression of corrective
gene, whereas periods of time. How can the genes be delivered and expressed to produce adequate
amouts of protein to correct disease? A majority of genes delivery strategies, both ex vivo and in vivo
rely on viruses as vectors to introduced therapeutic genes into cells.
The idea of a viral vector is to use a viral genome to carry a therapeutic gene or genes and to use the
virus itself to infect human body cell and introduce the therapeutic genes. Scientiest have considered
various viruses such as adenovirus, which cause the common cold; influenza viruses, which cause the flu;
and herpes viruses, which can cause cold sores and some cause sexually transmited disease, as potential
vectors for gene therapy. Even HIV has been considered as a gene therapy vectors. For any viral vector
to work, sscientists must br sure that these vectors have been genetically engineered so that they can
neither produce disease nor spread throughout the body and infect other tissues.
Most viruses infect human body cells by binding to and entering cells and then releasing their genetic
material into nucleus or cytoplasm of human cell. This is ussualy DNA but some viruses contain an RNA
genome. The infected human cell now serves as a host reproducing the viral genome and producing viral
RNA and proteins. Viral proteins ultimately assemble to create more viral particles that break out of te
host cells so that they are free to infect other cells and repear the life cycle.
It may seem strange that viruses would be even be considered for carrying genes to cure human
disease. However, scientist have realized that many harmful viruses are very effective at infecting
human cells and introducing their genome into cells. They reasoned that if these viruses could be
genetically altered to safety deliver therapeutic genes, then we could use viruses for beneficial
purposes. In many ways viruses are perfectly designed as gene therapy vehicles or cevectors for gene
therapy. For instance, adenovirus which most everyone has been infected by because it causes the
common cold can infect many types of body cells fairly efficiently. Retroviruses such as HIV are of
interest vectors because upon entering a host cells they copy their RNA genome into DNA and then
randomly insert their DNA into genome of the host cells where it remains permanently, a process called
intregation. One advantage of using retroviruses for gene delivery is thay they can integrate therapeutic
genes into DNA of human host cells, allowing permanent insertation of genes into the chromosomes of
a patients cell as a way to provide lasting gene therapy.
Viruses have also been widely studied as gene therapy vectors because some viruses only infect certain
body cells. This might allow for targeted gene therapy the ability to deliver genes only to the tissues
infected by certain viruses. For instance, a strain of herpes virus (HSV-1) primarily infected cells of the
cental nervous system. This strain is a candidate for targeted gene therapy of cells of the nervous system
which may be an effective way to treat genetic disorders of brain such as Alzheimers disease and
Parkisosns disease. Researches are also investigating ways that the genetically altered Herpes viruses
can be used to destroy brain tumors. Preliminary trials of this approach in human have shown some
promise.
Most human cells do not take up DNa easily because thein it could be possible to transfect cells by simpli
mixing then with DNA in tube in much the same way that transformation is achieved with bacterial cells.
However, some success has been demonstrated for both in vivo and ex vivo strategies using naked
DNA. Naked DNA is simply DNA by itself, without a viral vector that is infected directly into body tissues.
Small plasmid containing therapeutic genes are often used this approach. Cells of certain tissues will
take in some of the naked DNA an express genes delivery this way. Naked DNA delivery techniques have
been most effective in organs such as the liver and muscle. One of the major problems with transfecting
human cells in vivo is that because a relatively small number of cells take up the injected DNA, there
may not be enough cell expressing the therapeutic gene for gene therapy to have any affect on the
tissue. Scientist are working on ways to overcome thes problems and more effectively deliver naked
DNA.
One approach that may be a promising way to deliver DNA without viral vectors involves structures
called liposomes. Liposomes are small diameter, hollow particles made of lipid molecules, similar to fat
molecules present in cell membranes. Liposomes are packaged with genes and then injected into tissues
or sprayed. A similar technique involves coating tiny gold particles with DNA and then shooting these
particles into cells using a DNA gun. A DNA gun is really a pressurized air gun that delivers gold or
liposoms particles through cell membrane without killing most cells.
Another technology that scientist are experimenting with for delivering therapeutic genes involves
engineering and constructing artificial chromosomes. Ths technique involves making small
chromosomes that consist primarily of non-protein-coding DNA, which contains a therapeutic gene. The
key to this approach is that the artificial chromosome contains structure similar to normal human
chromosomes that allow for permanent incorporation into cells ad replication.