Treatment of Genetic Diseases

Question 1

What are 3 ways that treatment of single-gene disorders with loss-of-function mutations can be accomplished?

Answer 1

• replacing the defective protein
• improving its function
• minimizing the consequences of the deficiency

Question 2

What are 3 reasons that there is deficient treatment of genetic diseases?

Answer 2

• gene is not identified or pathogenesis is not understood
• prediagnostic fetal damage
• severe phenotypes are less amenable to intervention

Question 3

What are the treatment strategies for the level of intervention of a mutant gene?

Answer 3

• modification of the somatic genotype by transplantation or gene therapy
• pharmcological modulation of gene expression

Question 4

What is the treatment strategy for the level of intervention of mutant mRNA?

Answer 4

-RNA interference to degrade mutant mRNA

Question 5

What are the treatment strategies for the level of intervention of a mutant protein?

Answer 5

• protein replacement

- enhancement of residual function

Question 6

What is the treatment strategy for the level of intervention of metabolic or other biochemical dysfunctions?

Answer 6

-disease-specific compensation through diet or pharmacologics

Question 7

What is the treatment strategy for the level of intervention of clinical phenotypes?

Answer 7

-medical or surgical intervention

Question 8

What is the treatment strategy for the level of intervention of the family?

Answer 8

genetic counseling, carrier screening, or presymptomatic diagnosis

Question 9

What does ADA do?

Answer 9

converts adenosine to inosine and deoxyadenosine to deoxyinosine

Question 10

What is enzyme replacement therapy?

Answer 10

targeted augmentation of an intracellular enzyme

Question 11

What 2 lysosomal storage diseases is ERT used for?

Answer 11

Gaucher and Fabry Diseases

Question 12

What are limitations of ERT?

Answer 12

insufficient amounts of the infused enzyme is able to cross the blood-brain barrier and ERT is very expensive

Question 13

How does ERT work?

Answer 13

the human enzyme is modified by removing terminal sugars to expose core a-mannosyl residues which target the enzyme to mannose receptors on macrophages followed by delivery to the lysosome

Question 14

transfer of a diploid nucleus from an adult donor somatic cell, such as skin fibroblast, into an oocyte cytoplasm to generate a cloned embryo

Answer 14

nuclear transplantation

Question 15

use of embryonic stem cells generated by nuclear transplantation to form differentiated cell types of the body in culture

Answer 15

therapeutic cloning

Question 16

process of reimplanting an embryo obtained by nuclear transplantation into the uterus of a surrogate mother, with the purpose of allowing the embryo to develop into a human clone of the donor from whom the somatic nucleus was ontaimed

Answer 16

reproductive cloning

Question 17

target cell must undergo division for integration to occur and random integration into the host genome results in sustained expression of the gene carried by the vector

Answer 17

retroviruses

Question 18

infect a wide variety of dividing or nondividing cells -> can be obtained at high titer

Answer 18

adenoviruses

Question 19

widespread in humans so no adverse immune effects -> infect dividing or nondividing cells and can exist either episomally or stably integrated

Answer 19

adeno-associated virus