gene therapy

Question 1

what is gene therapy

Answer 1

Treatment of a disease by the transfer of genetic
material into a patient’s cells

Question 2

what is a type of x linked disease

Answer 2

haemophilia

Question 3

what is a type of autosomal recessive disease

Answer 3

sickle cell anaemia, cystic fibrosis

Question 4

what is an autosomal dominant disease

Answer 4

Huntington’s disease

Question 5

what diseases can be treated by gene therapy

Answer 5

cancers, cvd, infections, monogenic disease

Question 6

disadvantages of gene therapy

Answer 6

limited to somatic cells
specificity
side effects

Question 7

what is in vivo

Answer 7

put cells directly into a persons body

Question 8

what is ex vivo

Answer 8

remove cells
change it
amplify it
put it back into patients body

Question 9

what are types of viral vectors

Answer 9

Adenovirus (AV)
* Adeno-associated virus (AAV)
* Retrovirus (γ-retrovirus or lentivirus)
* Herpes simplex virus (HSV)

Question 10

what is one advantage and disadvantage of viral vectors

Answer 10

High expression but
high immunogenicity

Question 11

what are 3 gene therpay paradigms

Answer 11

Gene expression
Gene inhibition
Induction of cell death

Question 11

what is gene expression (increase)

Answer 11

Provide or generate a functional gene product

Question 12

what is gene inhibition (decrease)

Answer 12

Prevent expression of a gene product

Question 13

what is induction of cell death

Answer 13

By apoptosis or cytotoxic drug

Question 14

what paradigm is gene augmentation an example of?

Answer 14

gene expression (increase)

Question 15

when is gene augmentation used

Answer 15

Diseases caused by loss of gene function
e.g. inherited monogenic recessive disorders

Question 16

which paradigm is Generation of a functional gene

Answer 16

gene expression (increase)

Question 17

when is generation of a functional gene used

Answer 17

Disease caused by a non-functional protein because the gene
contains a mutation

Question 18

what mechanism are generation of a functional gene

Answer 18

Homologous recombination (HR)
Using gene editing (exogenous nucleases)
Exon skipping / exclusion

Question 19

when is exon skipping used

Answer 19

Disease caused by a non-functional protein because an exon
* is duplicated
* is deleted
* contains a frame-shift mutation
* contains a nonsense mutation

Question 20

what is the mechanism of exon skipping

Answer 20

Uses antisense oligonucleotides (ASO)
* Short synthetic single-stranded oligonucelotides
* Complementary to target mRNA
* Modified to prevent degradation by nucleases

Question 21

when is reducing gene expression used

Answer 21

Dominant disorder e.g. Huntington’s disease
* Autoimmune diseases
* Cancer caused by protein overexpression
* Infections

Question 22

what mechanisms can be used to reduce expression

Answer 22

Mechanisms?
* RNAi
* Antisense oligonucleotides
* Ribozymes
* Decoy strategy

Question 23

when is cell death used

Answer 23

Cancers
* Infections

Question 24

what mechanisms can cause cell death

Answer 24

Expression of suicide gene
* Transfer of pro-drug activator
* Immune cell activation marker