Gene Therapy and Its Potential Targeted Diseases Gene therapy is an innovative medical approach aimed at treating or preventing diseases by directly modifying the genetic material within a patient’s cells. This technique involves the introduction, removal, or alteration of specific genes to correct faulty genes responsible for disease development. Gene therapy is primarily delivered using vectors, often modified viruses, which carry the therapeutic genes into target cells. Non-viral delivery methods such as liposomes, nanoparticles, and CRISPR-Cas9-based gene editing are also being explored to enhance precision and safety. There are two main types of gene therapy: 1. Somatic Gene Therapy – Targets non-reproductive cells and affects only the treated individual. 2. Germline Gene Therapy – Involves changes in sperm or egg cells and can be passed on to future generations (currently controversial and not approved for human use in many countries). Techniques Used in Gene Therapy: Gene augmentation therapy: Adds a functional copy of the defective gene. Gene inhibition therapy: Inhibits the expression of a malfunctioning gene. Gene editing: Uses tools like CRISPR-Cas9 to correct specific gene mutations. Potential Targeted Diseases: Gene therapy holds promise for a wide range of genetic and acquired disorders, including: 1. Monogenic Disorders: Cystic Fibrosis: Caused by mutations in the CFTR gene. Hemophilia: Due to defective genes affecting blood clotting proteins. Sickle Cell Anemia & Thalassemia: Inherited blood disorders treated by editing hemoglobin genes. Severe Combined Immunodeficiency (SCID): One of the first successful gene therapy applications. 2. Cancer: Gene therapy can deliver tumor-suppressor genes, stimulate immune responses (e.g., CAR-T cell therapy), or increase sensitivity of cancer cells to treatments. 3. Neurological Disorders: Parkinson’s Disease: Gene therapy can enhance dopamine production or protect neurons. Spinal Muscular Atrophy (SMA): Recently treated using FDA-approved gene therapy drugs like Zolgensma. 4. Infectious Diseases: Gene editing is being explored to target viral genomes (e.g., HIV) within host cells to eliminate latent infections. 5. Ocular Diseases: Leber’s Congenital Amaurosis (LCA): A rare form of inherited blindness successfully treated with gene therapy. Challenges and Ethical Concerns: Immune reactions, vector toxicity, off-target effects, and high cost are major limitations. Ethical concerns include germline editing, potential misuse for enhancement, and unequal access to therapies.

1. POTENTIAL TARGET DISEASE FOR GENE THERAPY
PRESENTED BY:
Syed Faizan
M.Pharm (Pharmaceutics)
Vidyabharati College of Pharmacy, Amravati

2. ❖ Gene
❖ Approaches to correct defective gene
❖ Types of Gene Therapy
• Somatic cell gene therapy
• Germline gene therapy
❖ Targeted disease for Gene Therapy
CONTENTS

3. ❑ GENE
➢ A gene is a specific segment of DNA (deoxyribonucleic acid) that contains
the instructions for making a particular protein or a set of proteins. Genes
are the basic units of heredity and are passed from parents to offspring.
➢ Each gene carries the code for a specific trait, such as eye color, blood type,
or the ability to produce certain enzymes. Genes are located on
chromosomes within the cell nucleus.

4. ➢A gene is a part of DNA molecule, and humans have about 30,000
genes.
➢ Genes carry ‘instructions’ that allow the cells to produce specific
proteins such as enzymes.
DNA RNA Proteins

5. Mutation in genes
Changes in codon sequence
Altered transcription and translation
Defective protein synthesis
Disease

6. Approaches to Correct Defective Gene
1. Normal gene may be inserted into nonspecific location within genome
to replace defective one.
2. Abnormal gene can be swapped for normal gene through homologous
recombination.
3. Abnormal gene could be repaired through reverse mutation.
4. Regulation of particular gene could be altered.

8. ❑ SOMATIC CELL GENE THERAPY
➢ Somatic gene therapy involves inserting a healthy gene into the body’s non-
reproductive (somatic) cells to treat a disease. It targets specific tissues or organs, such
as muscles, lungs, or blood cells, without affecting the patient’s offspring.
➢ This type of gene therapy is commonly used for conditions like cystic fibrosis, certain
cancers, and inherited blood disorders. It is considered safe and ethically acceptable
compared to germline gene therapy.

9. ➢ Somatic cell gene therapy can be delivered either ex vivo (cells are removed,
modified, and returned) or in vivo (genes are directly introduced into the body).
➢ The goal is to correct or replace faulty genes causing illness. Since changes occur
only in the treated individual, they are not passed on to future generations.

11. ❑ GERMLINE GENE THERAPY
➢ Germline gene therapy involves making changes to the DNA in
reproductive cells (sperm, eggs, or embryos). These genetic changes are
permanent and can be passed on to future generations.
➢ The goal is to prevent inherited diseases before birth by correcting faulty
genes at the earliest stage. While it has the potential to eliminate genetic
disorders, it also raises ethical and safety concerns because it affects
future children who cannot consent.

12. EX-VIVO IN-VIVO
Here cells are modified outside
the body and then transfer back
again.
It involves direct delivery of
therapeutic gene (DNA) into
target site of particular tissue of
the patient.
It involves patient own cells for
culture and genetic correction &
then return back to patient.
Genes are changed in the cells
when the cells are still in the body
Called Ex-Vivo because cells are
treated outside the body.
Called In-Vivo because the gene
is transferred into the cell inside
patient body.

13. Targeted disease for gene therapy
➢ In patients with Cystic fibrosis, a protein called cystic fibrosis transmembrane
regulator (CFTR) is absent due to a gene defect.
➢ In the absence of CFTR chloride ions concentrate within the cells.
➢ This leads to the accumulation of sticky mucous in respiratory tract and lungs.
➢ Treated by in vivo replacement of defective gene byadenovirus vector.
❑ Cystic Fibrosis

14. Normal CFTR Channel Mutant CFTR Channel

15. ➢ Hemophilia is an inherited bleeding disorder where the blood doesn’t clot properly
due to missing or defective clotting factors, usually factor VIII (Hemophilia A) or IX
(Hemophilia B).
➢ It is typically caused by mutations on the X chromosome, making it more common
in males. Symptoms include prolonged bleeding and easy bruising.
➢ Gene therapy delivers functional copies of clotting factor genes, aiming to reduce or
eliminate the need for regular injections.
❑ Hemophilia

16. ➢ Sickle cell anemia is a genetic blood disorder caused by a mutation in the HBB gene,
which affects hemoglobin in red blood cells. The cells become sickle-shaped,
blocking blood flow and causing pain, fatigue, and organ damage.
➢ It is inherited in an autosomal recessive pattern. Gene therapy targets the faulty gene
to restore normal hemoglobin production or to activate alternative genes, offering
potential cures in early clinical success.
❑ Sickle Cell Anaemia

17. ➢ Type 1 diabetes is an autoimmune condition where the body’s immune system
attacks insulin-producing beta cells in the pancreas. . Although not directly inherited,
genetic factors like mutations in the HLA gene region increase the risk.
➢ Gene therapy research focuses on protecting or regenerating beta cells and modifying
immune responses. Experimental therapies aim to restore insulin production, but full
cures are still under development.
❑ Type 1 Diabetes

18. ➢ Inherited blindness refers to vision loss caused by genetic mutations affecting eye
development or function.
➢ These disorders damage the retina, leading to progressive vision loss or blindness.
Gene therapy has shown promising results, especially for RPE65-related blindness,
where a functional copy of the gene is delivered directly to retinal cells.
➢ The FDA-approved gene therapy Luxturna is a major breakthrough, offering
improved vision for certain inherited forms of blindness.
❑ Blindness

19. ➢ Chronic Granulomatous Disease is a rare inherited immune disorder where white
blood cells can’t effectively kill certain bacteria and fungi. It is caused by mutations in
genes like CYBB, which affect the NADPH oxidase enzyme needed to destroy
pathogens.
➢ As a result, the body forms granulomas—clusters of immune cells—causing frequent
infections and inflammation. CGD is often X-linked, affecting mostly males.
➢ Gene therapy aims to correct the defective gene in bone marrow stem cells, restoring
immune function. Clinical trials have shown promising results, offering hope for long-
term treatment or cure.
❑ Chronic Granulomas Disease

20. ➢ Severe Combined Immunodeficiency (SCID) is a life-threatening inherited disorder
where the immune system lacks functioning T and B cells, leaving the body
defenseless against infections. It is often caused by mutations in genes like IL2RG (X-
linked SCID) or ADA.
➢ Infants with SCID may appear healthy at birth but soon suffer severe infections.
Without treatment, it is usually fatal in early childhood.
➢ Gene therapy has shown success, especially for ADA-SCID and X-linked SCID, by
correcting the faulty gene in stem cells, enabling the immune system to function
properly and offering a potential cure.
❑ Severe Combined Immunodeficiency

21. ➢ Gene therapy for cancer is a cutting-edge approach that involves modifying a
patient’s genes or cells to fight cancer more effectively. Instead of directly killing
cancer cells.
➢ Main Strategies:
➢ CAR T-cell Therapy: T-cells are taken from the patient, modified to target cancer
cells, then infused back. Used in blood cancers like leukemia and lymphoma.
❑ CANCER

22. ➢ Suicide Gene Therapy: Genes are inserted into cancer cells to make them sensitive
to specific drugs that kill only those cells.
➢ Oncolytic Virus Therapy: Viruses are engineered to infect and destroy cancer cells
while sparing normal cells.
➢ Gene Editing (CRISPR/Cas9): Targets and corrects mutations driving cancer
growth.

23. PREVIOUS YEAR QUESTION
• Explain the potential target Gene Therapy for inherited disorder and Cancer
disease.

24. THANK YOU..