Gene

Therapy

MONIQUE IRA DELOS

REYES
RHEA MAE SYCHUA
Objectives:
 To define gene therapy
 To know the cell types used
 To know the methods used on how the gene therapy are
introduced in the body
 To enumerate the techniques used
 To list diseases that can be treated with Gene Theraphy
Gene therapy
 Introduction
of gene with the capacity to cure or
prevent the progression of a disease
 TheDNA is carefully selected to correct the
effect of a mutated gene that is causing
disease.
 Thetechnique was first developed in 1972 but
has, so far, had limited success in treating human
diseases.
Cell types
 Somatic gene therapy: transfer of a section of DNA
to any cell of the body that doesn’t produce sperm
or eggs. Effects of gene therapy will not be passed
onto the patient’s children.
 Germline gene therapy: transfer of a section of DNA
to cells that produce eggs or sperm. Effects of gene
therapy will be passed onto the patient’s children
and subsequent generations.
How is DNA transfer done?
A section of DNA/gene containing instructions for
making a useful protein is packaged within a vector,
usually a virus, bacterium or plasmid.
 The vector acts as a vehicle to carry the new DNA
into the cells of a patient with a genetic disease.
 Once inside the cells of the patient, the DNA/gene is
expressed by the cell’s normal machinery leading to
production of the therapeutic protein and treatment
of the patient’s disease.
How to introduce the genes ?
 Ex vivo strategy- Where the patients cells are cultured in
the laboratory, the new genes are infused in to the cells
and modified genes are administered back to the
patient.
 In situ strategy- where the carrier of the gene is injected
to the patient either intravenously or directly to the
tissues.
 In vivo strategy- where the vector is administered
directly to the cell.
Vectors
 Thedelivery of DNA into cells can be accomplished by
multiple methods.
 Viral- introduce their genetic material into the host cell,
tricking the host's cellular machinery into using it as blueprints
for viral proteins. (Ex. retroviruses, adenoviruses, herpes
simplex, vaccinia, and adeno-associated virus)
 Non-viral– lower levels of transfection and gene expression,
and thus have lower therapeutic efficacy. (Ex.naked
DNA, electroporation, the gene
gun, sonoporation, magnetofection, the use
of oligonucleotides, lipoplexes, dendrimers, and inorganic
nanoparticles)
Gene therapy techniques

 Gene augmentation therapy

 Gene inhibition therapy
 Killing of specific cells
Gene augmentation therapy
 This is used to treat diseases caused by a mutation that stops a
gene from producing a functioning product, such as a protein
 This therapy adds DNA containing a functional version of the
lost gene back into the cell.
 The new gene produces a functioning product at sufficient
levels to replace the protein that was originally missing.
 This is only successful if the effects of the disease are reversible
or have not resulted in lasting damage to the body.
 For example, this can be used to treat loss of function
disorders such as cystic fibrosis by introducing a functional
copy of the gene to correct the disease.
Gene inhibition therapy
 Suitable for the treatment of infectious diseases, cancer and inherited
disease caused by inappropriate gene activity.
 The aim is to introduce a gene whose product either:
 inhibits the expression of another gene
 interferes with the activity of the product of another gene.
 The basis of this therapy is to eliminate the activity of a gene that
encourages the growth of disease-related cells.
 For example, cancer is sometimes the result of the over-activation of
an oncogene(gene which stimulates cell growth). So, by eliminating
the activity of that oncogene through gene inhibition therapy, it is
possible to prevent further cell growth and stop the cancer in its
tracks.
Killing of specific cells
 Suitable for diseases such as cancer that can be treated by
destroying certain groups of cells.
 The aim is to insert DNA into a diseased cell that causes that cell to
die.
 This can be achieved in one of two ways:
 the inserted DNA contains a “suicide” gene that produces a highly toxic product
which kills the diseased cell
 the inserted DNA causes expression of a protein that marks the cells so that the
diseased cells are attacked by the body’s natural immune system.
 It is essential with this method that the inserted DNA is targeted
appropriately to avoid the death of cells that are functioning
normally.
Diseases Treated with
Gene Therapy
Gene Therapy for
Acquired Diseases
Cancer
Multiple gene therapy strategies have been
developed to treat a wide variety of cancers,
including suicide gene therapy, oncolytic
virotherapy, anti-angiogenesis and therapeutic
gene vaccines.
Neurodegenerative Diseases
Recent progress in gene therapy has allowed for
novel treatments of neurodegenerative diseases such
as Parkinson's Disease and Huntington's Disease, for
which exciting treatment results have been obtained
in appropriate animal models of the corresponding
human diseases.
Gene Therapy for Genetic
Disorders
Severe Combined Immune Deficiency (SCID)
SCID is also known as the bubble boy disease.
Affected children are born without an effective
immune system and will succumb to infections outside
of the bubble without bone marrow transplantation
from matched donors.
Chronic Granulomatus Disorder (CGD)
CGD is a genetic disease in the immune system that
leads to the patients' inability to fight off bacterial and
fungal infections that can be fatal.
Hemophilia
Patients born with Hemophilia are not able to induce
blood clots and suffer from external and internal
bleeding that can be life threatening. In a clinical trial
conducted in the United States , the therapeutic
gene was introduced into the liver of patients, who
then acquired the ability to have normal blood
clotting time.
 Summary:
 Gene therapy is used to introduce gene to cure a disease.
 Two types of cell types are somatic and germline gene therapy.
 Ex vivo, in situ, and in vivo strategy are used to introduced the
genes in the patient.
 Two types of vectors are viral and non-viral.
 Gene therapy techniques are gene augmentation therapy,
gene inhibition therapy and killing of specific cells.
References

 http://catalogue.pearsoned.co.uk/samplechapter/0131010115.pdf
 https://en.wikipedia.org/wiki/Gene_therapy
 https://www.yourgenome.org/facts/what-is-gene-therapy
 https://www.slideshare.net/namarta28/gene-therapy-12326904
 http://learn.genetics.utah.edu/content/genetherapy/success/
 http://annualmeeting.asgct.org/about_gene_therapy/diseases.php