Gene Therapy and Gene Therapy and Genetic CounselingGenetic Counseling

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 Therapy

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

Suicide Gene Therapy For Treating CancerSuicide Gene Therapy For Treating Cancer

Cancer “Vaccine”Cancer “Vaccine”

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

Genetic CounselingGenetic Counseling

• Approach is non-directiveApproach is non-directive

• TimingTiming– Prenatal counselingPrenatal counseling

– Counseling of a family when inherited Counseling of a family when inherited disorder has occurreddisorder has occurred