Gene therapy

Advances in biochemistry and molecular biology have helped to understand the genetic basis of inherited diseases.
Gene therapy was once considered a fantasy (imaginary).
It was a dream of the researchers to replace the defective genes with good ones and cure the genetic disorders.

1. Tapaeshawr Y Gene Therapy
Tapeshwar Yadav
(Lecturer)
BMLT, DNHE,
M.Sc. Medical Biochemistry

2. A Brief History of Gene Therapy
Advances in biochemistry and molecular
biology have helped to understand the genetic
basis of inherited diseases.
Gene therapy was once considered a fantasy
(imaginary).
It was a dream of the researchers to replace
the defective genes with good ones and cure
the genetic disorders.

3. Contd…
However, thousands of individuals have
already undergone human clinical trials.
 A great leap in medical science has taken
place on the 14
th
September 1990, when a girl
suffering from Adenosine deaminase
deficiency (Severe immunodeficiency) was
treated by transferring the normal gene for
adenosine deaminase.

4. What is Gene Therapy?
It is intracellular delivery of genes to generate
a therapeutic effect by correcting an existing
abnormality.
Only somatic gene therapy, by inserting the
new gene into somatic cell of the patient is
under trail.
Germ cell gene therapy is considered as
unethical.
NOTE:- Gene therapy is the process of inserting normal genes
into cells to treat diseases.

5. Gene therapy strategies
1.Gene augmentation therapy:-
A DNA is inserted into the genome to replace
the missing gene product.
2. Gene inhibition therapy:-
The antisense gene inhibits the expression of
the dominant gene.

7. Approaches for Gene Therapy
Two approaches to achieve gene therapy:-
1.Somatic cell gene therapy
2.Germ cell gene therapy

8. 1.Somatic cell gene therapy:
The non-reproductive (non-sex) cells of an organism
are referred to as somatic cells.
These are the cells of an organism other than sperm
or egg cells, e.g.- bone marrow cells, blood cells, skin
cells, intestinal cells.
At present, all the research on gene therapy is
directed to correct the genetic defects in somatic
cells.
It involves the insertion of a fully functional and
expressible gene into a target somatic cell to correct
a genetic disease permanently.

9. 2.Germ cell gene therapy:
The reproductive (sex) cells of an organism
constitute germ cell line.
Gene therapy involving the introduction of
DNA into germ cell is passed on to the
successive generations
Ethical and technical reasons, germ cell gene
therapy is not being attempted at present.

10. Types of gene therapy
Ex vivo gene therapy
involves the transfer of genes in cultured
cells (e.g., bone marrow cells) which are then
reintroduced into the patient.
In vivo gene therapy
the direct delivery of genes into the cells
of a particular tissue is referred to as in vivo
gene therapy

11. Technique of ex vivo gene therapy
Isolate cells with genetic defect from the
patient.
Grow the cells in nature.
Introduce the therapeutic gene to correct
gene defect
Select the genetically corrected cells and grow
Transplant the modified cells to the patient.

13. Vectors in Gene Therapy
 Viruses i.e. retroviruses
Human artificial Chromosomes
Bone marrow cells i.e. totipotent embryonic
stem cells

14. IN VIVO GENE THERAPY
Direct delivery of the therapeutic gene (DNA) into
the target cells of a particular tissue of a patient
constitutes in vivo gene therapy.
Gene delivery can be carried out by viral or non-viral
vector systems.
Success of in vivo gene therapy mostly depends on-
oEfficiency of the uptake of the remedial (therapeutic)
gene by the target cells.
oIntracellular degradation of the gene and its uptake by
nucleus.
oExpression capability of the gene.

19. Human Gene Therapy Trials
Disease Gene therapy
Severe combined immunodeficiency
(SCID)
Adenosine deaminase (ADA)
Cystic fibrosis Cystic fibrosis transmembrane
regulator (CFTR)
Familial hypercholesterolemiaLDL receptor
Thalassemia α- or β-globin
Sickle cell anaemia β-globin
Lech-Nyhan syndrome HGPRT
Breast cancer Multi drug resistance I
Short stature Growth hormone
Diabetes GLUT-2, glucokinase
Phenylketonuria Phenylalanine hydroxylase
Citrullinemia Arginosuccinate synthetase

20. FUTURE OF GENE THERAPY
Theoretically, gene therapy is the permanent
solution for genetic diseases.
But it is not as simple as it appears since gene
therapy has several inbuilt complexicities.
Gene therapy broadly involves isolation of a
specific gene, making it’s copies, inserting
them into target tissue cells to make the
desired protein.
The story does not end here.

21. Contd…
It is absolutely essential to ensure that the
gene is harmless to the patient and it is
appropriately expressed (too much or too
little will be no good).
Another concern in gene therapy is the body’s
immune system which reacts to the foreign
proteins produced by the new genes.

22. Contd…
The public, in general, have exaggerated
expectations on gene therapy.
The researchers, at least for the present, are unable
to satisfy them.
As per the record, by 1999 about 1000 Americans
had undergone clinical trails involving various gene
therapies.
Unfortunately, the gene therapist are unable to
categorically claim that gene therapy has
permanently cured any one of these patients!
Some people in the media have openly questioned
whether it is worth to continue research on gene
therapy!!

23. Contd…
It may be true that as of now, gene therapy due
to several limitations, has not progressed the way
it should, despite intensive research.
but a breakthrough may come anytime, and of
course, this is only possible with persistent
research.
And a day may come (it might take some years)
when almost every disease will have a gene
therapy, as one of the treatment modalities.
And gene therapy will revolutionize the practice
of medicine!