الفهرس 
STRUCTURE AND FUNCTION OF GENETIC MATERIALOnly 14 pages are availabe for public view
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Abstract
The progress in the field of gene therapy is a result of the
proper understanding of biotechnology and molecular
components of cells, which in turn led to treating many genetic
diseases and malignancies, such as hematological malignancies.
The successful application of gene therapy requires the
transfer of treating genes through viral or non-viral vectors for
transmission of genetic heridetary material (DNA) to the
patient; also these vectors can be used in the DNA vaccines to
stimulate the immune response of the patient.
The viral vectors studied for gene therapy, include:
adenoviruses, adeno-associated viruses, herpes simplex viruses,
retroviruses and lentiviruses.
In the treatment with adenovirus, the absence of integration
into the host cell’s genome should prevent the type of cancer
seen in the severe combined immunodeficiency trails. The
adeno-associated virus is not associated with human diseases
and allows effective long-term treatment, it is becoming a very
attractive vector for human gene therapy.
Herpes simplex virus type 1 (HSV-1) is a promising vector
for gene therapy applications. To be used as therapeutic agents,
HSV-1 vectors must meet the stringent criteria of high titer and
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purity. Thus, development of scalable, efficient HSV-1 vector
purification strategies is essential to advance HSV-1 vectors
into clinic.
Physical methods of plasmid delivery have revolutionized
the efficiency of non viral gene transfer, in some cases reaching
the efficiencies of viral vectors. In vivo electroporation
dramatically increases transfection efficiency for a variety of
tissues. Other methods such as pressure-perfusion and
ultrasound, also improve plasmid gene transfer. Alternatives
e.g., focused laser, magnetic fields and ballistic (gene gun)
approaches can also enhance delivery. As plasmid DNA
appears to be a safe gene vector system, it seems likely that
plasmid with physically enhanced delivery will be used
increasingly in clinical trials.
This essay was focused on using gene therapy for the
treatment of many diseases, such as hemophilia, thalasemia,
sickle cell disease diseases, immunodeficiency disorders and
metabolic storage diseases.
In hemophilia B, a simple intramuscular (IM) injection of
AAV vector can direct sustained therapeutic levels of factor IX
in mice. Levels of expression are vector dose-dependent and
reach a stable plateau 6–8 weeks after vector administration.
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Limb perfusion demonstrated longterm (>3years), robust
F IX expression (circulating levels of 4–14%) by muscledirected
gene transfer, resulting in nearly complete correction of
the bleeding disorder in hemophilic dogs.
In severe combined immunodificiencies, gene therapy for
adenosine deaminase defeciency was based on infusions of
autologous peripheral blood lymphocytes (PBL) or HSC
transduced ex-vivo with retroviral vectors encoding ADA.
Long-term follow up of children receiving PBL gene therapy
has demonstrated long-term persistence of gene corrected T
cells more than twelve years after the last infusion, without
adverse events. Gene therapy led to an improvement of cellular
and humoral responses, in the absence of enzyme replacement
therapy, with proven clinical benefits.
In cases of hematological malignancies, despite the use of
chemotherapy and bone marrow transplantation, only a little
improvement in survival rate over the past years was observed.
In such cases gene therapy has become an exciting mean for the
treatment of hematological malignancies because their
molecular bases have become largely understood.
Gene therapy for these malignancies can be achieved by
modifying the genetic defects associated with cancer by
introducing a gene that will trigger an anti-tumor immune
response, or modifying the immune response of the tumor by
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altering the effector function of immune system cells through
the transfer of an immune stimulatory gene into malignant cells.
Also the use of cytotoxic drug resistance genes to marrow
precursor cells may reduce the sensitivity of patient’s normal
cells to the effects of cytotoxic drugs.
Some discussion touched over the ethical, social and
religious issues surrounding gene therapy evoked, which
requires judicious use of this new direction of treatment. The
gene therapy, at present, is focused on correcting genetic
defects and treatment of life-threatening diseases. But inducing
genetic changes of the reproductive cells, which pass genes to
future generations, should be used only after good
understanding to the side effects, the ethical and religious
aspects in this field