Gene therapy involves introducing genes into cells to treat or prevent disease. It works by delivering a therapeutic gene into a patient's target cells using a vector. This can replace an abnormal gene with a healthy one, inactivate a mutated gene, or introduce a new gene to fight disease. There are two main types - somatic gene therapy only affects treated cells while germline gene therapy results in permanent changes that can be inherited. Approaches include ex vivo gene therapy, which modifies cells outside the body before transplant, and in vivo gene therapy through direct delivery. While gene therapy holds promise to cure genetic diseases, it faces challenges like short-lived effects and safety risks.

1. Gene therapies
Presented to: Dr. Javed Ali
SPER, JAMIA HAMDARD
Presented by: Dipak Kumar Gupta
M.Pharm 1st yr.(II sem)
Pharmaceutics

2. What is gene therapy
• Gene therapy is the introduction of genes into existing cells to prevent or cure a
wide range of disease
• 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 functioning improperly.
 Introducing a new gene into the body to help fight a disease.

4. How it works
• A vector delivers the therapeutic gene into a patients target cell
• The target cells become infected with the viral vector
• The vectors genetic material is inserted into the target cell
• Functional proteins are created from the therapeutic gene causing the cell
to return to a normal state.

5. Types of gene therapy
• Somatic gene therapy
• Germ line gene therapy

6. Types of gene therapies

7. Somatic gene therapy
• Affects only the targeted cells in the patient, and is not pass to future
generations.
• Short –lived because the cells of most tissues ultimately die and are replaced
by new cells
• 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 diseases.

8. Germ line 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 particular family.
• Also raises controversy:
• Some people view this type of therapy as unnatural, and like it to
“playing god”.
• Others have concerns about the technical aspects.

9. Approaches in gene therapy

10. Types of somatic cell gene therapy

11. Ex-vivo gene therapy
• Transplant the modified cells to the patient.
• Select genetically corrected cells and grow.
• Introduce the therapeutic genes .
• Grow the cells in culture Isolate cells with genetic defect from a patient

12. Ex-vivo gene therapy(process)

14. Example of ex-vivo gene therapy
• 1st gene therapy – to correct deficiency of enzyme, Adenosine deaminase
(ADA).
• Performed on a 4yr old girl Ashanthi DeSilva.
• Was suffering from SCID- Severe Combined Immunodeficiency.
• Caused due to defect in gene coding for ADA
• Deoxyadenosine accumulate and destroys T lymphocytes.
• Disrupts immunity , suffer from infectious diseases and die at young age.

15. In-vivo gene therapy
• Direct delivery of therapeutic gene into target cell into patients body.
• Carried out by viral or non-viral vector systems
• It can be the only possible option in patients where individual cells cannot be
cultured in vitro in sufficient numbers (e.g brain cells)
• In vivo brain transfer is necessary when cultured cells cannot be re-implanted in
patients effectively.

16. Examples of in-vivo gene therapy
• In patients with cystic fibrosis, a protein called cystic fibrosis trans-
membrane regulator (CFTR) is absent due to a gene defect.
• In the absence of CFTR chloride ions concentrate within the cells and it
draws water from surrounding.
• This leads to the accumulation of sticky mucous in respiratory tract and
lungs.
• Treated by in vivo replacement of defective gene by adenovirus vector

17. In-vivo gene therapy

18. METHODS OF GENE DELIVERY
PHYSICAL METHODS
 Gene Gun
• Employs a high-pressure delivery system to shoot tissue with gold or
tungsten particles that are coated with DNA
 Microinjection
• Process of using a glass micropipette to insert microscopic substances
into a single living cell.
• Normally performed under a specialized optical microscope setup called a
micromanipulator.

19. CHEMICAL METHODS
 USING DETERGENT MIXTURES
• Certain charged chemical compounds like Calcium phosphates are mixed
with functional cDNA of desired function.
• The mixture is introduced near the vicinity of recipient cells.
• The chemicals disturbs the cell membrane, widens the pore size and
allows cDNA to pass through the cell.
 LIPOFECTION
• It is a technique used to inject genetic materials into a cell by means of
liposomes.
• Liposomes are artificial phospholipid vesicles used to deliver a variety of
molecules including DNA into the cells.

20. GENE THERAPY
GENE AUGMENTATION THERAPY
• Most common form of gene therapy
• Foreign gene replaces missing or defective gene.
• Eg. Replacement of defective p53 gene by a normal one in liver cancer.
 GENE INHIBITION THERAPY
• Done to block the overproduction of some proteins.
• 2 types – Antigene and antisense therapy.
• Antigene – blocks transcription using antigene oligonucleotide
• Antisense – blocks transalation using antisense oligonucleotide

21. Contnd.....
• Long lasting therapy is not achieved by gene therapy; Due to rapid dividing
of cells benefits of gene therapy is short lived.
• Immune response to the transferred gene stimulates a potential risk to
gene therapy.
• Viruses used as vectors for gene transfer may cause toxicity, immune
responses, and inflammatory reactions in the host.
• Disorders caused by defects in multiple genes cannot be treated
effectively using gene therapy.
• Gene therapy has the potential to eliminate and prevent hereditary
diseases such as cystic fibrosis, ADA- SCID etc.
• It is a possible cure for heart disease, AIDS and cancer.
• It gives someone born with a genetic disease a chance to life.
• It can be used to eradicate diseases from the future generations.

22. ADVANTAGES
• Gene therapy has the potential to eliminate and prevent hereditary
diseases such as cystic fibrosis, ADA- SCID etc.
• It is a possible cure for heart disease, AIDS and cancer.
• It gives someone born with a genetic disease a chance to life.
• It can be used to eradicate diseases from the future generations.

23. DISADVATAGES
• Long lasting therapy is not achieved by gene therapy; Due to rapid dividing
of cells benefits of gene therapy is short lived.
• Immune response to the transferred gene stimulates a potential risk to
gene therapy.
• Disorders caused by defects in multiple genes cannot be treated
effectively using gene therapy.
• Viruses used as vectors for gene transfer may cause toxicity, immune
responses, and inflammatory reactions in the host.

24. references
• Dubey R.C, A textbook of biotechnology, 1st edition (2004), S Chand and
company, New Delhi
• Gupta P.K, Elements of Biotechnology, 1st edition(2001), Rastogi
Publications, Meerut.
• http://www.medindia.net/articles/genetherapy treatment.htm