Cell Biology Lecture 31: Gene Therapy

(Gene Therapy History) What year was the first case of gene therapy performed?

1990

(Gene Therapy History) What was the first disease treated with gene therapy?

Adenosine deaminase deficiency (ADA)

(Gene Therapy History) What deficiency did Jesse Gelsinger have?

OTC Deficiency

(Gene Therapy History) What was Jesse Gelsinger injected with?

Adenovirus

(Gene Therapy History) What did Jesse Gelsinger face within days?

Multi-system failure

(Gene Therapy Successes) What is the main disease that gene therapy is used for?

Cystic Fibrosis

(Gene Therapy Successes) What is an AR condition affecting chloride-ion channel

Cystic Fibrosis

(Gene Therapy Successes) What are the symptoms of cystic fibrosis?

1. Mucous secretion in lungs

2. Pancreatic insufficiency

(Gene Therapy Successes) What does mucous secretion in lungs lead to in cystic fibrosis?

1. Poor lung function

2. High risk for infection

(Gene Therapy Successes) What does pancreatic insufficiency lead to in cystic fibrosis?

1. Poor weight gain

2. Potential malnutrition

(Gene Therapy Successes) What was the first successful treatment of gating mutations in cystic fibrosis?

Kalydeco (Ivacaftor)

(Gene Therapy Successes) What is a possible mutation as a result of cystic fibrosis?

G551D gating mutation

(Gene Therapy Successes) How many individuals experience gating mutations during cystic fibrosis?

4%

(Gene Therapy Successes) What is gating mutation?

Mutation where cell surface proteins do not function properly and act like a locked gate

(Gene Therapy Successes) What did the Kalydeco (Ivacaftor) treatment lead to after cystic fibrosis?

1. Lung function improvement

2. Respiratory symptoms

3. Weight gain

(Gene Therapy Successes) What cystic fibrosis therapy is available for individuals who are homozygous ΔF508?

Lumacaftor/Ivacaftor combination therapy

(Gene Therapy Successes) What do ΔF508 mutations lead to?

Improper folding of CFTR

(Gene Therapy Successes) How much of the CFTR disease causing alleles is made up by ΔF508 mutations?

70%

(Gene Therapy Successes) If a patient has G551D mutations, is Lumacaftor or Ivacaftor more effective?

Ivacaftor

(Gene Therapy Limits) What are the limiting factors of gene therapy?

1. Ethical issues in early trials

2. Molecular roadblocks

(Gene Therapy Limits) What are the molecular roadblocks of gene therapy?

1. Finding an appropriate vector

2. Targeting a specific area/organ for delivery

3. Blood/brain barrier