gene therapy and genetic counseling. treating genetic diseases protein-based therapiesprotein-based...
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Treating Genetic DiseasesTreating Genetic Diseases
• Protein-based therapiesProtein-based therapies
DiseaseDisease Therapeutic AgentTherapeutic Agent
Cystic FibrosisCystic Fibrosis Digestive EnzymesDigestive Enzymes
HemophiliaHemophilia Clotting FactorClotting Factor
Treating Genetic DiseasesTreating Genetic Diseases
• Somatic Gene TherapySomatic Gene TherapyIntroducing functional genes into Introducing functional genes into somatic cells to provide a somatic cells to provide a nonheritable correctionnonheritable correction
Note: germ line therapy (altering Note: germ line therapy (altering gametes or fertilized eggs) is not gametes or fertilized eggs) is not being done for humansbeing done for humans
Target Sites for Gene TherapyTarget Sites for Gene Therapy
EndotheliumEndothelium Advantage: Can form capillaries to Advantage: Can form capillaries to secrete gene product into secrete gene product into bloodstreambloodstream
Example: clotting factor for Example: clotting factor for hemophilia hemophilia
SkinSkin Advantage: Can take small piece Advantage: Can take small piece of skin from patient to grow into of skin from patient to grow into large graftlarge graft
Example: Skin graphs can deliver Example: Skin graphs can deliver therapeutic proteinstherapeutic proteins
Target Sites for Gene TherapyTarget Sites for Gene Therapy
MuscleMuscle Advantage: Easily accessible, Advantage: Easily accessible, near bloodstreamnear bloodstream
Example: Treatment for Duchenne Example: Treatment for Duchenne Muscular Dystrophy Muscular Dystrophy
LiverLiver Advantage: Multiple functions, Advantage: Multiple functions, capacity to regeneratecapacity to regenerate
Example: Treatment for familial Example: Treatment for familial hypercholesterolemiahypercholesterolemia
Target Sites for Gene TherapyTarget Sites for Gene Therapy
LungsLungs Advantage: cells lining the Advantage: cells lining the passageways are easily passageways are easily accessible accessible
Example: aerosol spray to treat Example: aerosol spray to treat Cystic FibrosisCystic Fibrosis
Nervous Nervous TissueTissue
Advantage: ability to treat Advantage: ability to treat common illnesses and injuriescommon illnesses and injuries
Challenge: neurons do not divideChallenge: neurons do not divide
Example: gene therapy on Example: gene therapy on fibroblasts to allow them to fibroblasts to allow them to produce neurotransmittersproduce neurotransmitters
Applying Your KnowledgeApplying Your Knowledge
A.A. Which tissue has cells lining an accessible Which tissue has cells lining an accessible passageway? passageway?
B.B. Which tissue can regenerate?Which tissue can regenerate?
C.C. Which tissue has the advantage of Which tissue has the advantage of producing blood vessels? producing blood vessels?
1.1. LiverLiver2.2. EndotheliumEndothelium3.3. MuscleMuscle4.4. LungsLungs5.5. SkinSkin
Treating Genetic DiseasesTreating Genetic Diseases• Gene delivery methodsGene delivery methods
---Vectors---VectorsAdeno-associated Adeno-associated virusvirus
Small genesSmall genes
Long-term expressionLong-term expression
AdenovirusAdenovirus Large genesLarge genes
Transient expressionTransient expression
HerpesHerpes Long-term expressionLong-term expression
Infects nerve cellsInfects nerve cells
RetrovirusRetrovirus Long-term expressionLong-term expression
Infects dividing cellsInfects dividing cells
Methods of Introducing GenesMethods of Introducing Genes
• ex vivoex vivo: incorporate gene into cells : incorporate gene into cells outside the body and then deliver outside the body and then deliver altered cells to patient altered cells to patient
• in situin situ: vector carrying the gene is : vector carrying the gene is injected into localized and injected into localized and accessible body partaccessible body part
• in vivoin vivo: vector carrying the gene is : vector carrying the gene is introduced directly into the body, introduced directly into the body, often through a blood vesseloften through a blood vessel
Initial Gene Therapy TreatmentsInitial Gene Therapy Treatments• ADA deficiencyADA deficiency
– periodic treatment of white blood periodic treatment of white blood cells in older childrencells in older children
– treatment of stem cells from treatment of stem cells from umbilical cord blood in infantsumbilical cord blood in infants
Ashanti DaSilvaAshanti DaSilva
Andrew GobeaAndrew Gobea
Initial Gene Therapy TreatmentsInitial Gene Therapy Treatments• Ornithine Transcarbamylase Ornithine Transcarbamylase
(OTC) deficiency(OTC) deficiency
Jesse Gelsinger
Died from a massive immune response against
viral vector
Current Gene Therapy TreatmentsCurrent Gene Therapy Treatments• Canavan DiseaseCanavan Disease
– deficiency of aspartoacylase that leads deficiency of aspartoacylase that leads to destruction of myelin-producing to destruction of myelin-producing oligodendrocytesoligodendrocytes
– use of liposome or viral vector to use of liposome or viral vector to introduce gene into brain tissueintroduce gene into brain tissue
Max Randell
Applying Your KnowledgeApplying Your Knowledge
Identify the type of gene therapy used in each case.Identify the type of gene therapy used in each case.• For Andrew Gobea, ADA genes were introduced For Andrew Gobea, ADA genes were introduced
to his umbilical cord stem cells and these cells to his umbilical cord stem cells and these cells were delivered to his body. were delivered to his body.
• For Jesse Gelsinger, viruses containing the OTC For Jesse Gelsinger, viruses containing the OTC gene were introduced into an artery leading to his gene were introduced into an artery leading to his liver.liver.
• For Max Randell, viral particles with the For Max Randell, viral particles with the aspartoacylase gene were injected into his brain aspartoacylase gene were injected into his brain at six sites. at six sites.
1.1. ex vivoex vivo gene therapy gene therapy2.2. in situin situ gene therapy gene therapy3.3. in vivoin vivo gene therapy gene therapy
Genetic CounselingGenetic Counseling
• To help families understand and cope To help families understand and cope with genetic diseasewith genetic disease
• Provide information onProvide information on– Inheritance patternsInheritance patterns– Risk of inheriting a disease or recurrenceRisk of inheriting a disease or recurrence– Genetic tests and interpretation of resultsGenetic tests and interpretation of results– Available treatments for genetic disordersAvailable treatments for genetic disorders