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GENE
THERAPY
Presented to : Dr.Leslye Jhonson
Presented by: Khazeema Yousaf &
Maheen Alam
Biot 412: Medical Biotechnology
What is gene therapy?
How does gene therapy works?
Tools of Trade—Vector
What are the types of gene therapy?
Advantages and disadvantages of gene therapy
History
What is the current status of gene therapy?
what factors have kept gene therapy from becoming an effective treatment for genetic
disease?
WHAT IS GENE THERAPY?
• Gene therapy is a technique for correcting defective genes
responsible for disease development
• A normal gene may be inserted into a nonspecific location
within the genome to replace a nonfunctional gene. This
approach is most common.
• An abnormal gene could be swapped for a normal gene
through homologous recombination.
• The abnormal gene could
be repaired through
selective reverse mutation,
which returns the gene to
its normal function.
About one in ten
people has, or
will develop at
some later
stage, an
inherited genetic
disorder, and
approximately
2,800 specific
conditions =one
gene
• The regulation (the degree
to which a gene is turned
on or off) of a particular
gene could be altered
HOW DOES GENE THERAPY WORK?
For inserting DNA of interest scientists have to have
DNA delivery "vehicles" as vectors
They can be Viral and non viral-Tools of trade
Gene therapy can be exvivo or invivo.
TOOLS OF
TRADE-VECTORS
• Viral
• Non-viral
• Retroviruses = create
double-stranded DNA copies • Liposome=Circular piece of
dsDNA-plasmid packed into
of their RNA genomes. Then
liposome;not specific in
integrated into
targeting
chromosomes of host
DNA=dsDNA,not
• Adenoviruses =with double- • Naked
specific. Effectivness is low
stranded DNA genomes
but will not activate immune
• Adeno-associated viruses =
response
single-stranded DNA viruses,
insert their genetic material
at a specific site on
chromosome 19.
• Herpes simplex viruses
double-stranded DNA viruses
that infect a particular cell
type, neurons
TYPES OF GENE
THERAPY
advantages of viral vectors:
 good at targeting and entering cells.
 Some viral vectors might be engineered to target specific
types of cells.
 modified so that they can't replicate and destroy the cell.
drawbacks of viral vectors:
 A virus can't "expand" to fit a piece of genetic material
larger than it is naturally built to carry.
 can cause immune responses, resulting in two potential
outcomes:
Patients may get sick.
A patient's immunity to a virus may prevent him from responding to
repeated treatments.
HISTORY
initiated during the 1960s and early 1970s
In 1992 Doctor Claudio Bordignon--- performed the first procedure of
gene therapy using hematopoietic stem cells as vectors to deliver genes
intended to correct hereditary diseases. This was a world first.
In 1993 Andrew Gobea born wiith severe combined immunodeficiency
(SCID). Blood was removed from Andrew's placenta and umbilical cord
immediately after birth, containing stem cells. Retroviruses and stem
cells were mixed, after which they entered and inserted the gene into
the stem cells' chromosomes.
In 2003 a University of California research team inserted genes into the
brain using liposomes coated in a polymer called polyethylene glycol
(PEG).
In 2006 Scientists at the National Institutes of Health, successfully
treated metastatic melanoma in two patients using killer T cells
genetically retargeted to attack the cancer cells.
In May 2006 a team of scientists led by Dr. Luigi Naldin reported a
breakthrough for gene therapy in which they developed a way to
prevent the immune rejection usimg miRNA
On 1 May 2007 Moorfields Eye Hospital and University College
London's Institute of Ophthalmology announced the world's first
gene therapy trial for inherited retinal disease.
In September 2009, the journal Nature reported that researchers at
the University of Washington and University of Florida were able to
give trichromatic vision to squirrel monkeys using gene therapy, a
hopeful precursor to a treatment for color blindness in humans
WHAT IS THE CURRENT
STATUS OF GENE
THERAPY RESEARCH?
(FDA) has not yet approved any human gene
therapy product for sale. current gene
therapy is experimental and has not proven
very successful in clinical trial
Gene therapy suffered a major setback with the
death of 18-year-old jesse gelsinger. Having gene
therapy trial for ornithine transcarboxylase
deficiency (otcd). he died from multiple organ failures
4 days after treatment.
In january 2003, fda placed a temporary halt on all gene
therapy trials using retroviral vectors in blood stem cells.
In April of 2003 the FDA eased the ban on gene therapy
trials using retroviral vectors in blood stem cells.
The National Institutes of Health (NIH) also plays an
important role in ensuring the safety of gene therapy
research. NIH provides guidelines for investigators and
institutions (such as universities and hospitals) to follow
when conducting clinical trials with gene therapy.
Presently, gene therapies for the following
diseases are being developed:
cystic fibrosis (using adenoviral vector), hiv
infection (cell-based), malignant melanoma
(cell-based), duchenne muscular dystrophy
(cell-based), hemophilia b (cell-based), kidney
cancer (cell-based), gaucher's disease
(retroviral vector), breast cancer (retroviral
vector), and lung cancer (retroviral vector).
what factors have kept gene therapy from
becoming an effective treatment for genetic
disease?
Short-lived nature of gene therapy
Immune response
Problems with viral vectors
Multigene disorders
Questions??