CRISPR and CEP290
What does the CEP gene encode?
Ciliary protein
What does the RPE in the RPE65 stand for?
Retinal Pigment Epithelium
Electroretinogram (ERG)
Unlike Luxturnas gene addition, EDIT-101 relies on this genome editing mechanism
CRIPSR/Cas9 mediated gene editing
What does LCA stand for?
Leber Congenital Amaurosis
What is AAV Tropism?
Specific cell types within the eye that a particular AAV serotype can infect
What serotype AAV does Luxturna use?
AAV2
What is a key indicator of LCA on an electroretinogram?
A flat line/no peaks
Which therapy uses gene addition?
Luxturna
Why is AAV used for gene therapy delivery?
It's safe and can carry genetic material into cells
This protein facilitates strand invasion during HDR, enabling precise gene editing?
RAD51
In Luxturnas mechanism the viral vector enters RPE cells by this process
Endocytosis
What vitamin derivative is central to the visual cycle?
Vitamin A (retinoids)
Which repair pathway in CRIPSR is error prone?
NHEJ
What does an autosomal recessive disorder require for a person to be affected?
Two mutated copies of the gene (one from each parent)
What might happen if Cas9 mistakenly cut DNA in mitochondrial genes of retinal cells?
Causes further cell death and retinal degeneration
What accumulates in RPE cells when the RPE65 enzyme is nonfunctional?
all-trans retinyl esters
Why is timing important for treatment?
Dead photoreceptors cant be repaired - early treatment works best
The same Luxturna technique was attempted to be used for the CEP290 mutation. Why did this not work?
The intron sequence is too big for the same approach/AAV2 is too small for the gene
In Figure 2 we talked about the release of episomal DNA being released into the nucleus. what does episomal DNA mean?
Designed to remain separate from the host chromosomes, replicating independently within the cell's nucleus
What does CRISPR stand for?
Clustered Regularly Interspaced Short Palindromic Repeats
True or False: Luxturna replaces the mutated RPE65 gene permanently
False, it adds a functional copy
Why would someone who has the same diagnosis show different symptoms at different times?
They'd have a different mutation
Why is CRIPSR considered more risky then Luxturna?
Mistakes can’t be undone once the genome is changed
Why do scientists prefer the eye for testing gene therapy first?
It’s isolated from the rest of the body, lowering risk