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Flashcards in Muscle 5 Deck (18):
1

What are the features of adenovirus?

• Medium sized non-enveloped icosahedral virus
• Very large genome and carrying capacity
• Causes gastroentitis and conjunctivitis (mild diseases)
• Capable of transducing both proliferating and non-proliferating cells (low tropism for skeletal muscle)
• 35kb capacity

2

What are the features of 1st gen adenovirus?

Generated by substitutions of E1 and/or E3 with an expression cassette – carrying capacity of 8kb and elicit a significant immune response in vivo (due to still producing viral genes) – successfully used to deliver a mini-dystrophin gene to mouse muscle

3

What are the features of 2nd gen adenovirus?

Deletion of additional viral genes to result in carrying capcity of 10kb, elicited an immune response, both 1st and 2nd gens had leaky expression of viral genes leading to an immune response against the vector

4

What are the features of 3rd gene adenovirus?

Gutted adenoviral vectors, lack all viral genes, reduced immunogenicity and carrying capacity of 30kb. Demonstrated to deliver full length dystrophin via injection leading to functional improvement (still need high doses for effect and these high doses cause immune response)

5

What is the size, carrying capacity and disease cauding potential of lentivirus?

Meidum sized envelpoed retrovirus, 8kb capacity, can cause HIV

6

What is lentivirus capable of?

Transducing proliferating and non-proliferationg cells and integrating into the genome of the host cells

7

Does lentivirus work better in vitro or vivo?

In vitro - limited transduction in vivo

8

What does lentivirus present a high risk of?

Insertional mutagenesis - limits further treatment, may turn on cancerous gene

9

What delivery is not suitable for lentivirus and why?

Systemic - potential oncogenesis

10

What is adeno associated virus?

Small ssDNA parovirus

11

What % of the population has adeno associated virus infected?

80%

12

What does adeno associated virus need to replicate?

Presence of a helper virus

13

Why does adeno associated virus not cause disease in humans?

We are the natural host

14

What is the carrying capacity of adeno associated virus?

5kb

15

How is adeno associated virus generated?

Two-plasmid transfection system in the presence of viral helper genes

16

How many adeno associated virus serotypes and which ones can transduce the heart and skeletal muscle?

9
1,6,8,9

17

What is utrophin?

• Homologue of dystrophin and structurally similar (doesn't have ABD2 region)
• Normally expressed at the NMJ and overexpressed on the sarcolemma in the mdx mouse, thought to be compensating for the loss of dystrophin

18

What was the effect of AAV9?

Improved function in diaphragm but didn't improve fibrosis