Treatment of Genetic Diseases Flashcards
What are 3 ways that treatment of single-gene disorders with loss-of-function mutations can be accomplished?
- replacing the defective protein
- improving its function
- minimizing the consequences of the deficiency
What are 3 reasons that there is deficient treatment of genetic diseases?
- gene is not identified or pathogenesis is not understood
- prediagnostic fetal damage
- severe phenotypes are less amenable to intervention
What are the treatment strategies for the level of intervention of a mutant gene?
- modification of the somatic genotype by transplantation or gene therapy
- pharmcological modulation of gene expression
What is the treatment strategy for the level of intervention of mutant mRNA?
-RNA interference to degrade mutant mRNA
What are the treatment strategies for the level of intervention of a mutant protein?
- protein replacement
- enhancement of residual function
What is the treatment strategy for the level of intervention of metabolic or other biochemical dysfunctions?
-disease-specific compensation through diet or pharmacologics
What is the treatment strategy for the level of intervention of clinical phenotypes?
-medical or surgical intervention
What is the treatment strategy for the level of intervention of the family?
genetic counseling, carrier screening, or presymptomatic diagnosis
What does ADA do?
converts adenosine to inosine and deoxyadenosine to deoxyinosine
What is enzyme replacement therapy?
targeted augmentation of an intracellular enzyme
What 2 lysosomal storage diseases is ERT used for?
Gaucher and Fabry Diseases
What are limitations of ERT?
insufficient amounts of the infused enzyme is able to cross the blood-brain barrier and ERT is very expensive
How does ERT work?
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
transfer of a diploid nucleus from an adult donor somatic cell, such as skin fibroblast, into an oocyte cytoplasm to generate a cloned embryo
nuclear transplantation
use of embryonic stem cells generated by nuclear transplantation to form differentiated cell types of the body in culture
therapeutic cloning
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
reproductive cloning
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
retroviruses
infect a wide variety of dividing or nondividing cells -> can be obtained at high titer
adenoviruses
widespread in humans so no adverse immune effects -> infect dividing or nondividing cells and can exist either episomally or stably integrated
adeno-associated virus
