Gene therapy (stem cells)

Including:

What is gene therapy? 1. Retrovirus

2. Adenovirus
- An approach of treating diseases by either modifying the 3. Adeno - associated virus
expressions of an individual’s genes or correction of abnormal 4. Herpes simplex virus
genes.
RETROVIRUS VECTOR SYSTEM
History of gene therapy
- The recombinant retroviruses have the ability to integrate
1960’s: The concept of gene therapy was introduced. into the host genome.
- Can carry a DNA of size – less than 3.4kb
1972: Friedman and Roblin authored a paper in science titled “gene - Target cell – dividing
therapy for human genetic disease.”
ADENO VIRUS VECTOR SYSTEM
1984: a retrovirus vector system was designed that could efficiently insert
foreign genes into mammalian chromosomes.
- Adenoviral DNA does not integrate into the genome and is
1990: the first approved gene therapy in the US took place on 14 not replicated during cell division.
September 1990, at the national institute of health (NIH), under the - Humans commonly come in contact with adenovirus,
direction of William French Anderson. majority of patients have already developed neutralizing
antibodies which can inactive the virus.
1992: Doctor Claudio Bordignon performed the first procedure of gene - Target- non dividing cells.
therapy using hematopoietic stem cells as vectors to deliver genes
intended to correct hereditary diseases. ADENO ASSOCIATED VIRUS VECTOR

Types of Gene Therapy - It is a human virus.

- It is single stranded
Somatic cell gene therapy - AAV is enters host cell, becomes double stranded and gets
integrated into chromosome.
 Therapeutic genes transferred into the somatic cells. - AAV is not currently known to cause disease and
 E.g. Introduction 0f genes into bone marrow cells, blood cells, consequently the virus cause a very mild immune
skin cells etc. response
 Will not be inherited later generations - Target – non dividing, dividing cells.
 At present all researches directed to correct genetic defects in -
somatic cells. HERPES SIMPLEX VIRUS VECTOR
- Viruses which have natural tendency to infect a particular
Germ line gene therapy type of cell.
- The herpes simplex virus is a human neurotropic virus. This
 Therapeutic genes transferred into the germ cells. is mostly examined for gene transfer in the nervous system.
 E.g.. Gene introduced into eggs and sperms.
 It is heritable and passed on to later generations. History of stem cell
 For safety, and technical reasons, it is not being attempted at
 1999- first successful human transplant of insulin
present.
making cells from cadavers
Types of somatic cell gene therapy  2001- first cloned human embryos (only six cell
stage ) created by advanced cell technology
Ex vivo (USA)
 2004- Harvard researchers grow stem cells from
- Cells are modified outside the body and then transplanted back in embryos.
again (called ex vivo because the cells are treated outside the)
History of somatic cell nuclear transfer (cloning)
In vivo
- The first mammal cloned from adult cells was dolly, the
- Genes are changed in cells when the cells are still in the body sheep.
(called in vivo because the gene is transferred to cells)
HOW DOLLY THE SHEEP WAS BEEN CLONED?
VECTORS IN GENE THERAPY
Dolly was born on 5th July 1996 from three mothers. She
To transfer the desired gene into target cell, carrier is required. Such was created using the technique of somatic cell nuclear
vehicles of gene delivery are known as vectors. transfer. In these the cell nucleus from adult cell is
transferred into unfertilized oocyte. The initial attempt to
2 mean classes clone animal made from embryonic cell from which cell
from which DNA nucleus was extracted. The DNA nucleus
 Viral vectors was then implanted into unfertilized egg, from which
 Non-viral vectors existing nucleus been removed. A chemical shock
treatment was given to the egg, in order to simulate into
Ideal vector host mothers. The result was the cloned animal comes out
- TARGET the right cells to be genetically identical to the original cell. In 1996 a
- INTEGRATE the gene in the cells. sheep named DOLLY was the first mammal to be cloned
- ACTIVATE the gene. from somatic cell.
- AVOID harmful side effects.
- No universal vector exists.

Types of viral vectors Reporter: Amper, Marivic T. BEED-4B

A number of viruses have been used for human gene therapy, Rojo, Merry Jane T. BEED-4B
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