An Assignment on

Gene Therapy Related to Cancer,

AIDS & Hereditary Diseases
Prepared by: Anha Afrin Shefa
Student ID: MS-141111

What is Gene Therapy(GT)?

Gene therapy is an experimental technique that uses genes to
treat or prevent disease. In the future, this technique may
allow doctors to treat a disorder by inserting a gene into a
patients cells instead of using drugs or surgery.
Researchers are testing several approaches to gene therapy,
including:
---Replacing a mutated gene that causes disease with a healthy copy of the gene.

---Inactivating, or knocking out, a mutated gene that is functioning improperly.

---Introducing a new gene into the body to help fight a disease.

Gene therapy was first conceptualized in 1972.

The first FDA-approved gene therapy experiment in the United
States occurred in 1990, when Ashanti DeSilva was treated for ADASCID (Adenosine deaminase deficiency- severe combined
immunodeficiency)

Techniques of Gene Delivery

Types of Vectors

Gene transfer by Natural

methods are- Gene
conjugation, Bacterial
transformation, Retroviral
transduction,
Agrovbacterium mediated
transfer.
Physical methods includesMicroinjection and Biolistics
transformation.
Chemical methods areDNA transfer by calcium
phosphate,
Liposome mediated transfer.
Electrical MethodElectroporation.

GT for Treatment of Cancer

Cancer causes cells to grow aberrantly. The growth of

cancer cells leads to damage of normal tissues, causing
loss of function.
It is better to have a way of treating the cancer by
repairing the faulty genes or better yet replacing
them with functional genes so that the routine gene
functions are revived. Gene therapy is a way of repairing
genetic problems.
This can be achieved by adding a functional copy of
the defective gene. When a functional copy of a faulty
gene is added, the tissues and organs that might have
been affected by the gene mutations will begin to function
in the right way.
The gene therapy works better because unlike other cancer
treatments that only treat the symptoms it goes deeper
correcting all the genetic problems.

Strategies of GT for Cancer

Insertion of "sensitivity" or suicide' gene into the tumor- by

introducing the gene that encodes HSVtk (thymidine kinase gene of the
Herpes simplex virus)

Blockage of the expression of oncogenes- by introducing the gene

that encodes antisense K-RAS message.
Killing tumor cells by inserting toxin genes under the control of a
tumor-specific promoter
Protection of stem cells from the toxic effects of chemotherapythrough introduction of the gene that confers MDR-1 (multiple drug
resistance type 1)

Insertion of a wild-type tumor suppressor gene, for example P53 or

the gene involved in Wilm' tumor.
Blockage of the mechanisms by which tumors evade immunological
destruction, for example by introducing the gene that encodes
antisense IGF-1(insulin-like growth factor-1) message.
Enhancing the immunogenicity of the tumor by introducing genes
that encode foreign antigens.
Enhancing immune cells to increase anti-tumor activity by
introducing genes that encode cytokines.

Telomerase, Suicide and Oncolytic Gene

Therapy Approaches

Efficacy of GT over Conventional

Chemotherapy and Cell Protection

Enhancing
immunogenicity of the
tumor

Tumor cells are surgically removed from the

patient, growing them in tissue culture and
inserting immunostimulatory genes in
vitro.

These cells are then re-injected into the

patient in an effort to induce a significant
systemic immune response that will both
destroy tumor cells and protect the patient
against a recurrence of the tumor.

Alteration of syngeneic tumors with the

genes that encode IL-1 b, IL-2, IL-4, IL-6,
TNFa, or r-interferon results in immunological
destruction of the tumor cells in vivo.

Enhancing immune
cells to increase antitumor activity

T lymphocytes have the

capacity to hone in on
tumor tissue. This property
has been used to deliver
cytokines directly to tumor
masses for human gene
therapy.
The secretion of cytokines
locally at the tumor site by
the effector T cell will
enhance their anti-tumor
activity and avoid the sideeffects that result from the
systemic administration of
cytokines.

Gene Therapy for Treatment of AIDS

In addition to improving existing antiretroviral
therapy, there are ongoing efforts to discover
alternative approaches for treatment of
HIV/AIDS.
One promising alternative approach is gene
therapy, in which a gene is inserted into a cell
to interfere with viral infection or replication.
Other nucleic acid-based compounds, such as
DNA, siRNA, RNA decoys, ribozymes and
aptamers or protein-based agents such as
fusion inhibitors and zinc-finger nucleases can
also be used to interfere with viral replication.

Gene therapy by
Early efforts in gene therapy
vector
forlentiviral
AIDS have been
focused on
viral vectors as the delivery of
combination of 3 different
inhibitory genes in a single
lentiviral vector that utilizes
stem cells in the delivery
process. Scientists reported
that cell-derived gene transfer
is safe and biologically active
in HIV-infected individuals.
But, the use of viral vectors for
gene delivery poses problems
such as toxicity,
immunogenicity, insertion
mutagenesis and limitations
with scale-up procedures.
These problems have
encouraged the investigation
of non-viral vectors for gene

NANOTECHNO
LOGY

(A) Inhibit entry and

fusion by interfering with
production of receptors or
co-receptors
(B) Interfere with
translation and
transcription of viral
genes preventing
production of proteins
and genomic RNA.

NANOTECHNOL
OGY

RNAi affects (A) various cellular targets involved in viral infection

such as CD4, CCR5, and/or CXCR4, the major cell surface coreceptors responsible for viral entry or (B) the various stages of the
viral replication cycle. HIV replicates by reverse transcription to
form DNA and uses the DNA to produce copies of its mRNA for protein

Huntington's
Disease

Cystic
Fiborsis

Hereditary
Disease..
disorder that
inherited
Main
culprit is aa defective
geneisthat
causes genetically.
mucus and
other bodily fluids to be far more viscous than they
should be. Repeated respiratory infections, trouble
breathing, severe digestive problems, diabetes and liver
failure.
Transferring the normal CFTR gene into the affected
epithelium cells would result in the production of
functional CFTR in all target cells, without adverse
reactions or an inflammation response. Multiple
approaches have been tested for gene transfer, such as
liposomes
andis viral
vectors
models
and
The culprit
a mutated
gene in
on animal
the patient's
fourth
clinical
trials. Bothcausing
methods
found
to cells
be relatively
chromosome
the were
brain's
nerve
to
inefficient
treatment
options.
progressively
and
irreparably break down. The
defective gene causes a piece of DNA to be
duplicated many more times than it should
Gene silencing aims to reduce the production of the
mutant protein, since HD is caused by a single
dominant gene encoding a toxic protein. This
experiments in mouse models have shown that
when the expression of mHtt is reduced, symptoms

Gene Therapy for Hereditary Disease

Continued..
Hemophilia
It is a sex linked inhetitance disease with a group of disorders -hemophilia A, B and C-that make it difficult for a person's blood
to clot. Each of the three disorders is linked to a lack of a specific
clotting factor. Someone with hemophilia lacks the associated
clotting factor -- factor VIII for hemophilia A, factor IX for
hemophilia B and factor XI for hemophilia C
Gene therapy involves insertion of theF9gene into an
adeno-associated virus-8 vector, The transduced virus is
infused intravenously. After treating six people with hemophilia in
early 2011 with this technique, two years later all of the patients
Sickle
cell anemia
were producing
blood plasma
clotting factor.

In this condition, a patient's red blood cells

sometimes form a tough, sickle-like shape, which
can cause them to get stuck in blood vessels.
HSC(Hematopoietic stem cells) from patient's
own blood is a alternative to current SCD
treatments as it creates a self-renewing normal
blood cell by inserting beta-globin gene that has
anti-sickling properties through lentivirus into
HSC. This approach avoids the risk of rejection of
donor cells.

Gene Therapy for Hereditary Disease

Continued..
Duchenne muscular dystrophy
It encompasses involuntary and voluntary
muscles damages and become weaker over time.
It is possible to repair the gene associated with
causing
DMD
through
the
use
ofmeganucleaseenzymesthough significant work
remains until it can be tested in human patients.
Biostrophinis a gene delivery vector.
Chronic granulomatous disease(CGD)
It is a diverse group of hereditary diseases in which
certain cells of the immune system have difficulty
forming the reactive oxygen compounds used to kill
certain ingested pathogens.
Gene
transfer
into
hematopoietic
stem
(HSC)/progenitor cells has resulted in the long-term
correction of immune and metabolic defects in treated
patients. In most cases, successes were augmented by a
recognized biological selection for successfully treated

Thanks to All

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