gene therapy

Question 1

outline the gene therapy applied for colour vision deficiency in squirrel monkeys

Answer 1

• gene therapy used to treat adult squirrel monkeys with red/green colour vision deficiency
• needed 2 opsin genes to view both red and green
• males only had one opsin gene, females had 2 of the same opsin gene
• missing gene was introduced into retina via injection and treated in 20 weeks

Question 2

what are the 4 ethical issues associated with gene therapy

Answer 2

1. originality of normal DNA
2. preservation of the germ line
3. access and expense
4. risk vs benefit

Question 3

outline the 2 types of gene therapy (3)

Answer 3

1. germ-line therapy
   - treats sperm or ova
   - all cells of the individual and subsquent generations altered
   - banned
2. somatic cell therapy
   - treats individual only
   - single organ/tissue altered
   - current therapy

Question 4

what prevents gene therapy from being an effective treatment for diseases (4)

Answer 4

1. short-lived nature
   - unless the gene integrated is inserted into stem cells, there is no long-term cure
2. immune response
   - reduces effectiveness
   - makes repeated applications difficult
3. viral vector problems
   - toxicity
   - immune and inflammatory responses
4. multigene disorders
   - the most commonly occuring disorders are too difficult to treat effectively using gene therapy (bc single organ/tissue)

Question 5

outline adeno-associated viruses (AAV) -> (3)

Answer 5

• AAV is a vector that delivers DNA to target cells with little or no immune response
• lacks viral genes and can be engineered to contain DNA sequences of interest
• one of the safest, most recent gene therapy strategy

Question 6

identify an occular AAV used

Answer 6

AAV5

- trophic for photorecptors (feeds nutrients)

Question 7

outline Leber’s Congenital Amaurosis (1+4)

Answer 7

• an inherited degenerative condition present from birth
• a key protein in the visual cycle (RPE65) is non-functional
• > causes a loss of 11-cis-retinal
• > children appear to have alternate pathway for 11-cis-retinal but diminishes with age
• > results in blindness

Question 8

outline gene therapy for age-related macular degeneration (AMD) -> (2)

Answer 8

• gene therapy aimed at stopping dry AMD was completed first time this year
• can only prevent worse, can’t cure

Question 9

outline gene therapy for monogenic disorders (4)

Answer 9

• in monogentic disorders, a single gene defect is responsible
• comprises of less than 3% of human diseases
• due to direct loss of protein function
• treatment is to transfer correct gene and correct expression at the correct location