Lecture 14 Flashcards
How is skin colour caused? What cells do this and where are they found?
Melanocytes are cells found in skin epidermis, the eye, inner ear, meninges, bones and heart and these act to produce melanin, the destruction of these leads to melanoma.
The amount of melanin pigment determines the colour of skin and the producting of melanin is activated by UV.
What is melanoma? What is a possible treatment option? (how come?)
melanoma is a malignant tumour of melanocytes (a mole is a benign overgrowth), the two risk genes (which if different from normal with have increased risk) are MCR1 and tyrosinase, though most cases are sporadic. Stage 4 melanoma can be treated with monoclonal antibodies which act against PD1 or CTLA4 (this prevents the tumour from protecting itself from T cells) to increase the lifespan of affected individuals.
What is the production pathway for melanin? What happens if there is any problem?
It is produced from the molecule tyrosine which is converted to Dopa which is converted to Dopaquinone, then to dopachrome and then to melanin. If there is any problem in this pathway the individual will have albinoism.
How does gene therapy work? How do we make it safe.
Gene therapy is a single treatment which can supply a replacement gene for the life of the cell. We use viruses as vectors for this because they are very efficient at getting the DNA into the cell (specialised mechanisms for cell entry, expression of their genome, DNA replication and cell exit). The viral vectors have been engineered to use the ability of a virus for cell entry and gene expression, but remove the DNA replication and cell exit capabilities for safe efficient gene delivery. Different viruses have different pros and cons e.g Lentiviruses like HIV are good at inserting into the genome.
What is Leber congenital amaurosis? what is a treatment option?
Leber congenital amaurosis is a rare disorder which has visual impairment which gets worse as they age, they have increased sensitivity to light, involuntary eye movements and extreme farsightedness. It occurs in 2 to 3 per 100,000 newborns and at least 14 different genes are associated but the RPE65 mutations are among the most common. There are no current treatments but a possibility is gene therapy, with injections targeting the retina.
What is CRISPR-Cas? What are the other two options for gene editing
CRISPR-Cas is a system borrowed from the bacterial defense system, it can be used to cut out, insert or replace genes anywhere in the genome, it can be used to treat genetic diseases by editign embryos or create mutations to model disease in animal models.
Gene editing involves being able to correct the genetic defect rather than simply inserting a replacement gene. These involve using zinc fingr nucleases, talens (uses proteins to correct genome) and CRISPR-Cas (uses DNA to correct the genome).
How does HIV infection work? How does HIV gene therapy work?
The steps in HIV infection are receptor binding, fusion with the cell membrane, uncoating, reverse transcription of the RNA to DNA, integration of this DNA into the DNA of the cell (creating a provirus section), translation of viral RNA, assembly of the virus, budding from the cell membrane and then maturation of the virus.
HIV gene therapy involves infecting stem cells of the patient, growing them in the lab and returning them to the patient where they are now resistant to HIV.
