Lecture 52: Treatment of Genetic Disorders

Question 1

PKU I vs PKU II

Answer 1

PKU I - problem with enzyme (PAH)

PKU II - problem with coenzyme

Question 2

What does PKU exhibit?

Answer 2

Locus heterogeneity

Question 3

What must people with urea cycle disorder avoid?

-What do you give to scavenge the N?

Answer 3

Protein in their diet bc of the N that can be provided, also avoid stress.

-give Benzoic Acid –> Hippurate (diverts ammonia to glycine synthesis)

Question 4

Hemophilia A (replacement therapy)

Answer 4

-Factor VIII therapy is really effective

Question 5

How do you stabilize a protein for protein replacement therapy?

Answer 5

PEGylation of protein stabilizes it (tag with carbohydrate group)
-improve half life of the protein

Question 6

How do you get symptomatic improvement in the patient with Gaucher disease?

Answer 6

-Exposure of mannose residue allows lysosomal uptake

Question 7

What are the 2 therapeutic targets of cancer cells?

Answer 7

1. Ph+ Chronic Myeloid Leukemia
   -Tyrosine kinase inhibitor
   (Gleevec/Imanitib mesylate)
2. Her2+ breast cancer
   - Her2 Antibodies (Herceptin)

Question 8

What do you do for therapy for HBS (sicking crisis)? What would you give them for treatment?

Answer 8

Increase Gamma Hb

-inhibit histone deacetylation (give Hydroxyurea)

Question 9

Is morally and ethically unacceptable

Answer 9

• Germline gene therapy

- Somatic cell gene therapy can only be done

Question 10

Delivery Methods of Gene therapy (adenoviruses vs. retroviruses)

Answer 10

Adenovirus (extrachromosomal)
-the protein might get degraded by the cellular machinery

Retroviruses

• gene can be inserted in inappropriate places
• Gene was put into the chromosome

Question 11

Liposome Mediated Gene Therapy

Answer 11

• DNA approach

- Immune response can result in tissue damage

Question 12

What are 2 problems with Gene Therapy?

Answer 12

1. Immune response

2. Tumor formation

Question 13

What uses an adenovirus as a vector for p53?

Answer 13

Gendicine

Question 14

CRISPR-Cas9 technology

Answer 14

Genes can be inserted/edited with more ease and better precision

Question 15

IPSCs (Pluripotent stem cells)

Answer 15

Key idea: is that differentiated cells may be reverted back to the undifferentiated state

Question 16

miRNA and siRNA

Answer 16

• regulate gene expression (antisense therapy)

- miRNA is processed into siRNA and that binds to mRNA to silence translation or its degradation

Question 17

miRNA and cancer “cure”

Answer 17

1. Insert miRNA to bind to oncoprotein

Question 18

What are other names for siRNA therapy?

Answer 18

Antisense therapy or RNA interference

Question 19

For PKU, how do you treat it?

Answer 19

• Give product, not substrate

- Give cofactor/coenzyme