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Flashcards in Unit 7 - Treatment Deck (30)
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how should you treat people with mutant genes?

modify somatic genotype
-gene therapy


how should you treat people with mutant mRNA?



how should you treat people with mutant PRO?

protein replacement or enhancement of residual function


how should you treat people with metabolic or biochemical dysfunction?

disease specific compensation


how should you treat people with clinical phenotypes?

medical or surgical interventions


how should you treat families of people with genetic mutations?

genetic counseling, carrier screening, and prenatal testing


what does drug therapy usually do for genetic mutations?

usually just treats the symptoms, for entire life


what are surgical treatments?

-transplantation (heart, liver, etc.)
-repair (cleft lip/palate, aorta, bone fusion, etc.)


how are metabolic disorders treated?

-dietary modification/restriction
-replacement (add back PRO that is missing)
-diversion (use other pathways to avoid accumulation of metabolite, or redirect to breakdown substances to harmless compounds)
-inhibition (modifying rate of synthesis by using a drug or other agent that slows/blocks a critical step in pathway)
-depletion (removal of a substance in excess)


how is hereditary hemochromatosis treated?

accumulation of Fe in liver that is controlled by regular, life-long phlebotomies


methods of treatment at the protein level

-replacement (extracellular; if protein is absent, add it back)
-replacement (intracellular; must target specific cell type)
-enhancing genetic expression (use one gene to compensate for the mutation in another)


how is hemophilia A treated?

replacement of factor VIII


how is alpha-1 antitrypsin deficiency treated?

replacement of alpha 1 antitrypsin


what are some problems with using extracellular protein replacement as a treatment?

-antibody production in patient


how is Gaucher disease treated?

lysosomal storage disease with deficiency of glucocerebrosidase
-treat by replacing the enzyme


how is sickle cell anemia treated at the protein lvel?

enhance genetic expression
-treatment with decitabine increases levels of y-globin in blood (hypomethylates DNA by inhibiting methyltransferase)
-Hb F is replacement O2 carrier and inhibits polymerization of deoxyhemoglobin S


what would bone marrow transplantation be used for?

1. hematologic disorders
-remove disease clone and replace it with unaffected cells
-collect BM stem cells from patient (autologous) or matched donor (allogenic)
-transplanted cells reestablish in new host
--if autologous, may not get all of disease out
2. lysosomal storage diseases
-BM is about 10% of body's cell mass, and extracellular transfer from normal marrow may stimulate function in other cells
-acts as source of mononuclear phagocytes
-can reduce size of various internal organs
-if done within first 2 years of life, will limit negative neurological impact of disease


what are embryonic stem cells potential therapy for and a potential source of cells for?

1. Parkinson and Alzheimer's disease
2. tissue grafting and organ transplants


what are problems with allogenic stem cell use?

1. immunosuppression (subject to it for life)
2. graft VS host diease


what are potential ill effects and potential benefits of cloning/nuclear transfer?

1. negative impact on genes, Xm, normal cellular processes (aging)
2. benefits for agriculture (improve crops, herds, etc.)


how is gene therapy used nowadays?

"deliberate introduction of genetic material into human somatic cells for therapeutic, prophylactic, or diagnostics purposes"
-incorporate "normal" functioning genes into the genome


what are the general classes of gene therapy?

1. correct a loss of function mutation by incorporating a functional gene(s) into the genome
2. compensate for a deleterious dominant allele by replacing or inactivating the mutant allele
3. adding genetic material that has a pharmacological effect


what are requirements for successful gene therapy?

1. identification of gene
2. availability of gene sequence or cloned DNA from gene of interest
3. identification of target tissue
4. ability to deliver gene to target
5. understanding of gene biochemistry
6. understanding of expression


what's a major limitation of gene therapy?

delivery of gene to target
-vector must be able to carry the DNA
-must be able to insert DNA into target cell
-most permanent if the therapy DNA is incorporated into the host cell's own DNA (otherwise, once the therapy cells die, the gene therapy is lost)
-temporary incorporation in cytoplasm requires repeated therapy sessions (make artificial liposomes and fill with DNA, which fuses with target cell)


in vivo VS ex vivo

in: cloned gene is put directly inside patient

ex: cloned genes are gene transferred into patient's own cells, which are cultured
-select cells with the cloned gene, and return them to the patient


what was the first successful gene therapy and how was it treated?

ADA deficiency (immunodeficiency disorder that makes up 15% of SCIDs)
-viral vector that carried ADA cDNA was inserted into patient's T cell with LASN
-culture the ones that kept the infection, and infuse back into patient


what does ADA deficiency cause?

deoxyadenosine --> NH3 + deoxyinosine
-PNP enzyme: deoxyinosine --> xanthin oxidase --> uric acid --> urine
-if no ADA, deoxyadenosine --> dATP --> lymphocyte cell death


what is antisense DNA therapy?

useful to downregulate protein production
-cancer characterized by overproduction of a protein
-incorporate an antisense strand in the cells to block translation


what is RNA interference?

targeted degradation of mRNA
-destroy mRNA from negative dominant mutations, while leaving second allele alone
-reduce concenration of an mRNA that is overexpressed


what is AAV?

adeno-associated virus
-non-pathogenic vector
-reduces likelihood of an immune reaction
-is found on many serotypes, so the proper vector can be matched to a particular cell type
-non-integrative, so will not disrupt cancer genes

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