1. Gene Therapy and Genetic Counseling

2. Treating Genetic Diseases Protein-based therapiesProtein-based therapies Disease Therapeutic Agent Cystic Fibrosis Digestive Enzymes Hemophilia Clotting Factor

3. Treating Genetic Diseases Somatic Gene TherapySomatic Gene Therapy Introducing functional genes into somatic cells to provide a nonheritable correction Note: germ line therapy (altering gametes or fertilized eggs) is not being done for humans

4. Target Sites for Gene Therapy

5. Endothelium Advantage: Can form capillaries to secrete gene product into bloodstream Example: clotting factor for hemophilia Skin Advantage: Can take small piece of skin from patient to grow into large graft Example: Skin graphs can deliver therapeutic proteins

6. Target Sites for Gene Therapy Muscle Advantage: Easily accessible, near bloodstream Example: Treatment for Duchenne Muscular Dystrophy Liver Advantage: Multiple functions, capacity to regenerate Example: Treatment for familial hypercholesterolemia

7. Target Sites for Gene Therapy Lungs Advantage: cells lining the passageways are easily accessible Example: aerosol spray to treat Cystic Fibrosis Nervous Tissue Advantage: ability to treat common illnesses and injuries Challenge: neurons do not divide Example: gene therapy on fibroblasts to allow them to produce neurotransmitters

8. Applying Your Knowledge A.Which tissue has cells lining an accessible passageway? B.Which tissue can regenerate? C.Which tissue has the advantage of producing blood vessels? 1.Liver 2.Endothelium 3.Muscle 4.Lungs 5.Skin

9. Treating Genetic Diseases Gene delivery methodsGene delivery methods---Vectors Adeno-associated virus Small genes Long-term expression Adenovirus Large genes Transient expression Herpes Long-term expression Infects nerve cells Retrovirus Long-term expression Infects dividing cells

10. Methods of Introducing Genes ex vivo: incorporate gene into cells outside the body and then deliver altered cells to patientex vivo: incorporate gene into cells outside the body and then deliver altered cells to patient in situ: vector carrying the gene is injected into localized and accessible body partin situ: vector carrying the gene is injected into localized and accessible body part in vivo: vector carrying the gene is introduced directly into the body, often through a blood vesselin vivo: vector carrying the gene is introduced directly into the body, often through a blood vessel

11. Initial Gene Therapy Treatments ADA deficiencyADA deficiency –periodic treatment of white blood cells in older children –treatment of stem cells from umbilical cord blood in infants Ashanti DaSilva Andrew Gobea

12. Initial Gene Therapy Treatments Ornithine Transcarbamylase (OTC) deficiencyOrnithine Transcarbamylase (OTC) deficiency Jesse Gelsinger Died from a massive immune response against viral vector

13. Current Gene Therapy Treatments Canavan DiseaseCanavan Disease –deficiency of aspartoacylase that leads to destruction of myelin-producing oligodendrocytes –use of liposome or viral vector to introduce gene into brain tissue Max Randell

14. Applying Your Knowledge Identify the type of gene therapy used in each case. For Andrew Gobea, ADA genes were introduced to his umbilical cord stem cells and these cells were delivered to his body.For Andrew Gobea, ADA genes were introduced to his umbilical cord stem cells and these cells were delivered to his body. For Jesse Gelsinger, viruses containing the OTC gene were introduced into an artery leading to his liver.For Jesse Gelsinger, viruses containing the OTC gene were introduced into an artery leading to his liver. For Max Randell, viral particles with the aspartoacylase gene were injected into his brain at six sites.For Max Randell, viral particles with the aspartoacylase gene were injected into his brain at six sites. 1.ex vivo gene therapy 2.in situ gene therapy 3.in vivo gene therapy

15. Suicide Gene Therapy For Treating Cancer

16. Cancer “Vaccine”

17. Genetic Counseling To help families understand and cope with genetic diseaseTo help families understand and cope with genetic disease Provide information onProvide information on –Inheritance patterns –Risk of inheriting a disease or recurrence –Genetic tests and interpretation of results –Available treatments for genetic disorders

18. Genetic Counseling Approach is non-directiveApproach is non-directive TimingTiming –Prenatal counseling –Counseling of a family when inherited disorder has occurred