1. Gene Therapy Contemporary Issue – Genetic Disorders and Gene Therapy
Lesson Goals
To understand the nature of genetic diseases.
To differentiate between chromosomal and single gene diseases.
To understand the nature of Down Syndrome and diagnostic methods to detect it.
To understand the important points of heredity including dominant and recessive alleles.
To understand how to predict heredity using a Punnett square.
To understand the nature and heritability of Huntington Disease, Cystic Fibrosis, and Sickle Cell Disease.
To understand the nature of genetic testing and it’s future application to diagnose diseases and the probability of getting genetic diseases.
To understand the nature of gene therapy and it’s future application to cure diseases.
Key Terms;
chromosome chromosomal disease meiosis nondisjunction Down syndrome karyotype amniocentesis autosomal disease gene allele dominant recessive co-dominant widow’s peak genotype phenotype Huntington disease cystic fibrosis sickle cell disease

2. Genetics & Human Diseases
About 4,000 human diseases are thought to be inherited.
Scientists are making good progress figuring out where genes are located on chromosomes.
Genetic diseases are caused by mutations, or incorrect sequences, in the normal form of the gene.
Main Idea(s) of This Slide -
Genetic testing involves looking at the genes that code for certain traits. If certain alleles are found that cause diseases, scientists can identify whether a person will have the disease or carry the trait for the disease. There are currently tests for of the diseases that are thought to be inherited. Scientists can identify the “faulty” alleles on the chromosomes very early in development either from cells taken through amniocentesis or by testing cells from embryos intended for implantation through in-vitro fertilization.

3. What is Gene Therapy?
Gene therapy is a treatment or cure for disorders caused by mutated genes.
It involves adding a normally functioning copy of the gene(s) to enough affected cells to restore normal function.
Gene therapy is a treatment or cure for diseases caused by defective genes.

4. What is Gene Therapy
Germline gene therapy would be the permanent transfer of a gene into sperm or egg cells.
Future generations would be “cured”.
Somatic cell (body cell) gene therapy is transfer of a section of DNA to any cell of the body that doesn’t produce sperm or eggs.
- Effects of gene therapy will not be passed onto the patient’s children

5. Gene Therapy Successes
Although no gene therapies have been approved by the FDA for sale, some diseases have been experimentally successful:
Melanoma (skin cancer)
Severe Combined Immunodeficiencies
Hereditary Blindness
Sickle Cell Anemia

6. Adenoside Deaminase (ADA) Deficiency
ADA-deficient persons are affected by severe immunodeficiency, with recurrent infections that might be life-threatening.
First disease approved for gene therapy.
Autosomal recessive disorder.
The drug exists but is very expensive, needs to be injected in vein for life.

7. Video “bubble boy” https://www.youtube.com/watch?v=-G_SW8LmidA
Gene therapy cure bubble baby

8. How is it done? Viral Vector Carrying Healthy Gene
Cell with mutated gene(s)
Vector inserts healthy gene into cell
New gene in the cell along with original genes
Functional proteins are created from the therapeutic gene causing the cell to return to a normal state.

9. Gene Therapy
To design and carry out a gene therapy treatment, a researcher must:
Identify the gene(s) responsible for the disorder.
Make copies of the normal gene.
Insert the copies into vectors.
“Infect” the affected cells with the vectors.
Activate the gene so that transcription and translation take place.

10. Viruses as Vectors Replicate by inserting their DNA into a host cell
Gene therapy can use this to insert genes that encode for a desired protein to create the desired trait
Four different types
Adenovirus
Adeno-Associated Virus (AAV)
Retrovirus
Herpes Simplex Virus (HSV)

11. Viruses Adenoviruses: Common causes of respiratory illness
Adeno-Associated Virus: Is not currently known to cause disease, but can cause a milld immune response
Retrovirus: Any of a group of RNA viruses that insert a DNA copy of their genome into the host cell in order to replicate e.g. HIV
Herpes simplex virus: cause watery blisters in the skin or mucous membranes of the mouth, lips, nose or genitals

13. Vector Advantages and Disadvantages
Adenovirus
Infects many cell types
Does not integrate into host genome and can be lost.
Adeno-Associated Virus (AAV)
Integrates into host genome and cannot be lost
Difficult to work with.
Retrovirus
Integrates into host genome and can cause cancer
Herpes Simplex Virus (HSV)
DNA stays in nucleus without integrating into host genome.
Only infects cells of the nervous system.

14. Gene therapy techniques
Gene augmentation therapy
This is used to treat diseases caused by a mutation that stops a gene from producing a functioning product, such as a protein
This therapy adds DNA containing a functional version of the lost gene back into the cell
It is only successful if the effects of the disease are reversible or have not resulted in lasting damage to the body

15. Gene therapy techniques
Gene inhibition therapy
Suitable for the treatment of infectious diseases, cancer and inherited disease caused by inappropriate gene activity
The aim is to introduce a gene whose product either:
Inhibits the expression of another gene
Interferes with the activity of the product of another gene

16. Gene therapy techniques
Killing of specific cells
Suitable for diseases such as cancer that can be destroying certain groups of cells
This can be achieved in one of two ways:
The insert DNA contains a “suicide” gene that produces a highly toxic product which kills the diseased cell
The inserted DNA causes expression of a protein that marks the cell so that the diseased cells are attacked by the body’s natural immune system

18. Challenges of gene therapy
Delivering the gene to the right place and switching it on:
Delivering a gene into the wrong cell would be inefficient and could also cause health problems
Even once the right cell has been targeted, the gene has to be turned on
Cell sometimes obstruct this process by shutting down genes that are showing unusual activity

19. Challenges of gene therapy
Avoiding the immune response:
This is usually done by using vectors that are less likely to trigger an immune response
Making sure the new gene doesn’t disrupt the function of other genes
The cost of gene therapy