Lecture 5: TREATMENT OF GENETIC DISEASE

Question 1

Treatment of Metabolic Disorders

Answer 1

Dietary mod/restriction, replacement, diversion, inhibition, depletion

Question 2

Treatment at the protein level (include examples)

Answer 2

Extracellular replacement (ex Hemophilia A, a1-antitrypsin), Intracellular repl (Gaucher), enhancing genetic expression (sickle cell HbF).

Question 3

Remove the disease clone and replace it with

unaffected cells to treat hematologic disorders is called?

Answer 3

Bone marrow transplantation.

Question 4

Bone marrow transplantation can be used to treat [blankblank] diseases bc bone marrow is a source of mononuclear phagocytes, and if done within the first 2 years of life, will limit the negative neurological impact of these diseases.

Answer 4

Lysosomal storage diseases.

Question 5

Self renewing, undifferentiated cells that can proliferate and produce a wide variety of different types of
differentiated cells.

Answer 5

Stem cells.

Question 6

Problems with Allogeneic Stem Cell Use

Answer 6

Immunosuppression required, risk of GHD.

Question 7

“The deliberate introduction
of genetic material into human somatic
cells for therapeutic, prophylactic, or
diagnostics purposes.” This is definition of what type of therapy?

Answer 7

Gene therapy

Question 8

Gene therapy can correct for what, by incorporating a functional gene(s) into the genome? What else can it compensat for/ help with?

Answer 8

A loss of function mutation. Can replace or inactive a dominant deleterious mutation. Can add genetic material that has a pharm effect.

Question 9

List the requirements for successful gene therapy

Answer 9


Identification of gene

Availability of gene sequence or cloned
DNA from the ge
ne of interest

Identification of target tissue

Ability to deliver gene to target

Understanding of gene biochemistry

Understanding of expression

Question 10

Major limitation in gene therapy success so far? What’s the best scenario for it to work?

Answer 10

Delivery of Gene to Target. The vector must be able to carry the DNA, attach and insert. Best scenario is to transfer the DNA/gene into the target cell and stably integrate it into the cells’ DNA. That should be a permanent fix with the new gene being transmitted to all daughter.
cells.

Question 11

Antisense DNA therapy is a fairly straightforward and reasonably effective tool. Antisense RNA
will bind to its homologous sequence and prevent binding of ribosomes, etc., thus blocking
translation. Do you understand this?

Answer 11

Ok.

Question 12

Explain RNAi

Answer 12

RNAi targets mRNA and cuts it up, thus preventing production of abnormal proteins. The active
unit (siRNA – small interfering RNA) can be injected or incorporated into cells via vectors.