Lect 6: Treatment of Genetic Dz Flashcards
Medical or Surgical Intervention
drugs- tx the symphoms
Treatment of Metabolic disorders- at the protein level
- DIET!
- Replacement- add back something that is missing extracellular; intracellular involves
- Diversion- use other pathways to avoid accumulation of a metabolite
- Inhibition-modifying the rate of synthesis
- Depletion-removal of excess substance
- Enhancing genetic expression -use one gene to compensate for the mutation in another (as in increasing HbF production)
Transplantation
provides the possibility of eradicating the dz clone and returning the individual to health; bone marrow transplantation
Stem cells (2 types)
Embryonic - pluripotent and are capable of differentiating into any cell type
==Somatic - self renewing but can differentiate into the cell types present in the tissue of origin
Problems with Allogeneic Stem Cells
immunosuppression and GVHD
Induced Pluripotent Stem Cells -iPS
cells taken from an adult and are subjected to reprogramming factors that reverses differentiation. They can then be transplanted back
Cloning is taking a cell from one individual and growing up another identical individual. The closest thing to cloning is
nuclear transfer
Nuclear transfer
a single cell is obtained from a donor and an unfertilized egg is obtained from another individual. The oocyte is enucleated and the nucleus from the donor cell is inserted into another. This cell is now transplanted into a surrogate mom who will carry it to term.
IVF, ICSI, 3 parent fertilization
take the nucleus from a patient who has a mitochondrial disorder, transfer it to a health egg from another patient then it is reimplanted where the sperm comes to fertilize it.
Gene Therapy
is used to
==>correct for a loss of function mutation by incorporating a functional gene into the genome
==>compensate for a deleterious dominant allele by replacing or inactivating the mutant allele
==>adding genetic material that has pharmacological effect
In order for gene therapy to work
the specific gene responsible for a dz must be identified and its sequence clone must be available. A strategy must be in place to deliver the gene to the target tissue or cells. It is necessary to understand both the gene biochemistry. All necessary mechanisms must be transferred with the gene itself because once it gets into the target cells, it must be transcribed and translated for the therapy to work.
Primary limitation
getting the DNA to the target cells and having it stably incorporate into a stem line. Best case scenario is to transfer the DNA into the cell then to stably integrate it into the cell’s DNA.
Liposomes
the lipid bilayer of the liposome will fuse with the cell membrane and the DNA will be released into the cytoplasm. This is a temporary repair as the DNA will likely be degraded or it will be lost when the cell dies.
In vivo
genes are incorporated into vectors and targeted to specific cells in the body
Ex vivo
cells are extracted from the patient and genetically modified then returned to the patient
Antisense DNA Approaches
running RNA interference - targeted degredation of mRNA which destroys the mutations while leaving the second allele along. it reduces the conc of the mRNA that is overexpressed
Adeno-associated virus (AAV)
Reduces the likelihood of an immune reaction- does not integrate so it will not disrupt cancer genes
Germ-line therapy is not used
they are sticking with somatic cell studies
