WHAT IS GENE THERAPY ?
• Definiton: an experimental technique for correcting defective
genes that are responsible for disease development
• The most common form of gene therapy involves inserting a
normal gene to replace an abnormal gene
• Other approaches used:
Replacing a mutated gene that causes disease with a
healthy copy of the gene.
Inactivating, or “knocking out,” a mutated gene that is
Introducing a new gene into the body to help fight a disease.
• Researchers are studying gene therapy for a number of
diseases, such as
Severe combined immuno-deficiencies (SCID)
HISTORY AND DEVELOPMENT
OF GENE THERAPY
• 1960: The concepts of Gene Therapy was introduced
• 1970: Friedmann and Roblin author of a paper in Science titled "Gene
therapy for human genetic disease?” cite the first attempt to perform
The first approved gene therapy case at the National Institute of
Health, U.K. It was performed on a four year old girl named
Ashanti DaSilva. It was a treatment for a genetic defect that left
her with an immune system deficiency
New gene therapy approach repairs errors in messenger RNA
derived from defective genes. This technique has the potential to
treat the blood disorder Thalassaemia, Cystic fibrosis, and some
Sickle cell disease is successfully treated in mice
• 1992: Doctor Claudio Bordignon working at the Vita-Salute San Raffaele
University, Milan, Italy performed the first procedure of gene therapy using
hematopoietic stem cells as vectors to deliver genes intended to correct
• 1999: Death of Jesse Gelsinger in a gene-therapy experiment resulted in a
significant setback to gene therapy research in the United States
• 2006: Scientists at the National Institutes of Health (Bethesda, Maryland) have
successfully treated metastatic melanoma in two patients. This study constitutes
one of the first demonstrations that gene therapy can be effective in treating
• 2007- 2011: Research is still ongoing and the number of diseases that has been
treated successfully by gene therapy increases.
• 2011: Medical community accepted that it can cure HIV as in 2008, Gero Hutter
has cured a man from HIV using gene therapy
Result in permanent changes.
Potential for offering a permanent therapeutic
effect for all who inherit the target gene.
Possibility of eliminating some diseases from a
Also raises controversy:
Some people view this type of therapy as
unnatural, and liken it to "playing God”.
Others have concerns about the technical
Affects only the targeted cells in the
patient, and is not passed to future
Short-lived because the cells of most tissues
ultimately die and are replaced by new
Transporting the gene to the target cells or
tissue is also problematic.
Appropriate and acceptable for many
disorders, including cystic fibrosis, muscular
dystrophy, cancer, and certain infectious
BASIC PROCESS OF
1. VIRAL VECTOR
2. NON VIRAL VECTOR
GT utilizes the delivery of DNA into cells, which can be
accomplished by a number of methods.
The two major classes of methods :
recombinant viruses – VIRAL VECTOR
naked DNA or DNA complexes – NONVIRAL VECTOR
Viruses have evolved a way of encapsulating and
delivering their genes to human cells in a pathogenic
manner. Scientists have tried to harness this ability by
manipulating the viral genome to remove disease-
causing genes and insert therapeutic ones .
Virus bind to their hosts and introduce their genetic
material into the host cell.
Plausible strategy for gene therapy, by removing the
viral DNA and using the virus as a vehicle to deliver
the therapeutic DNA.
The viruses used are altered to make them safe,
although some risks still exist with gene therapy.
TYPES OF VIRUS
Many GT clinical trials rely on retroviruses or
adenoviruses to deliver the desired gene.
Other viruses used as vectors include adeno-associated
viruses, lentiviruses, pox viruses, alphaviruses, and
Differ in how well they transfer genes to the cells they
recognize and are able to infect, and whether they alter
the cell’s DNA permanently or temporarily
Are a tool commonly used by molecular biologists to
deliver genetic material into cells.
Can be performed in vivo or in vitro.
Viruses have evolved specialized molecular
mechanisms to efficiently transport their genomes
inside the cells they infect.
Delivery of genes by a virus is termed transduction
and the infected cells are described as transduced.
NON VIRAL VECTOR
Methods of non-viral gene delivery have also been
explored using physical (carrier-free gene delivery)
and chemical approaches (synthetic vector-based
Physical approaches, including
employ a physical force that permeates the cell
membrane and facilitates intracellular gene transfer
I. NAKED DNA
The simplest method of non-viral transfection.
Clinical trials carried out of intramuscular injection
of a naked DNA plasmid have occurred with some
success; however, the expression has been very low
in comparison to other methods of transfection.
This success, however, does not compare to that of
the other methods, leading to research into more
efficient methods for delivery of the naked DNA
such as electroporation and the use of a "gene gun",
which shoots DNA coated gold particles into the cell
using high pressure gas.
THAT ENHANCE THE
DELIVERY OF GENE THERAPY
-lipoplexes & polyplexes-
DNA must be protected from damage & its entry
into the cell must be facilitated
Plasmid DNA can be covered with lipids in an
organized structure like a micelle or a
liposome complexed with DNA it is called a
3 types of lipids:
anionic (negatively charged)
cationic (positively charged)
Initially, anionic and neutral lipids :
-were used for the construction of lipoplexes for
-but,there is little toxicity associated with them,
-they are compatible with body fluids
-there was a possibility of adapting them to be
-they are complicated turned to the cationic
Cationic lipids, due to their positive charge,
-naturally complex with the negatively
-their charge they interact with the cell membrane
-endocytosis of the lipoplex occurs
-DNA is released into the cytoplasm.
-The cationic lipids also protect against
degradation of the DNA by the cell.
Common used of lipoplexes
In gene transfer into cancer cells, where the
supplied genes have activated tumor
suppressor control genes in the cell
decrease the activity of oncogenes.
useful in transfecting respiratory epithelial cells,
so they may be used for treatment of genetic
respiratory diseases such as cystic fibrosis.
Complexes of polymers with DNA are called
consist of cationic polymers and their production
is regulated by ionic interactions.
large difference compared to lipoplexes is that
polyplexes cannot release their DNA load into
End= co-transfection with endosome-lytic
agents such as inactivated adenovirus must
occur (to lyse the endosome that is made during
endocytosis, the process by which the polyplex
enters the cell)
SUCCESS CASES OF GENE
GENE THERAPY CURES BLINDNESS
Cure blindness of inherited condition
Leber’s conginetal amaurosis
- inherited disease caused by an
abnormality in a gene called RPE65.
- The condition appears at birth or in the first
few months of life and causes progressive
worse and loss of vision.
HOW IT WORKS??
used harmless viruses
enable access to the cells beneath the
retinas of patients
By using a very fine needle
-safe in an extremely fragile tissue and can
improve vision in a condition previously
considered wholly untreatable.
SUCCESS CASES OF GENE
GENE THERAPY REDUCES PARKINSON’S
it significantly improved the weakness of the
symptoms such as tremors, motor skill problems, and
Main- overactive brain region: the subthalamic
nucleus should be introduced with gene
that would produce GABA—an inhibitory
chemical—then they could potentially quiet that
brain region and alleviate tremors.
HOW IT WORKS??
Done with local anesthesia, used a harmless,
inactive virus [AAV-2 GAD]
Deliver the GAD gene into patient’s
The gene instructs cells to begin making
GABA neurotransmitters to re-establish the
normal chemical balance that becomes
dysfunctional as the disease progresses
• Give a chance of a normal life to baby born with
• Give hope of healthy life to cancer patient.
• For certain disease that do not have any cure
except gene therapy, it could save many lives
ADVANTAGES OF GENE THERAPY
• The genetic testing, screening and research in finding the
availability of certain gene is very controversy.
• May increase rate of abortion if prenatal test regarding baby
with genetic disease is done.
• The cost is very high and the patient might need an insurance to
cover the treatment.
• Cosmetic industry may monopolized this gene therapy if it is
used in enhancing beauty and in vanishing the aging effect,
rather than used for treatment of a disease.
ETHICAL QUESTIONS SURROUNDING
• How can “good” and “bad” uses of gene therapy be
• Who decides which traits are normal and which constitute
a disability or disorder?
• Will the therapy only benefit the wealthy due to its high
• Could the widespread use of gene therapy make the
society less accepting of people who are different?
• Should people be allowed to use gene therapy to enhance
basic human traits such as height, intelligence, or athletic
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