12. Gene Therapy

Question 1

what is gene therapy

Answer 1

A medical approach that treats or prevents disease by correcting the underlying genetic defect

Question 2

SCID

Answer 2

commonly referred to as bubble boy disease

Question 3

SCID gene therapy trial

Answer 3

in Paris
treated 11 boys
- 9 cured
- 4 of these developed leukemia 3-6 years later
- 1 died
- FDA paused trials

Question 4

what was the first gene therapy approved in Europe

Answer 4

• treats ultra rare Lipoprotein Lipase Deficiency
• cost: over 1mil per patient
• drug withdrawn in 2017 due to high costs and rarity of patient

Question 5

Spinal Muscular Atrophy

Answer 5

• SMN1 protein is necessary for normal motor neuron function
• mutation of SMN1 gene leads to irreversible deterioration of motor neurons in spinal cord

Question 6

Zolgensma

Answer 6

• treats Spinal Muscuar Atrophy (SMA) type 1
• does not cure the disease but helps halt progression
• babies can breath without a ventilator
• can crawl and even walk

Question 7

Dystrophic Epidermolysis Bullosa

Answer 7

a rare genetic skin disorder where the skin becomes fragile and prone to blistering

Question 8

Luxturna

Answer 8

a gene therapy medication used to treat inherited retinal diseases caused by mutations in the RPE65 gene.

Question 9

what is the ultimate aim of gene therapy

Answer 9

to change gene expression in relevant cells so that disease symptoms are cured or reduced without any adverse effects

Question 10

somatic gene therapy

Answer 10

introducing genetic material into the cells of an individual’s body to treat or prevent disease. It targets non-reproductive cells and does not alter the individuals germ cells or affect their offspring

Question 11

germline gene therapy

Answer 11

modifying genetic material of reproductive cells with the goal of passing the genetic modifications onto future generations

Question 12

mitochondrial DNA replacement therapy

Answer 12

replacing defective mitochondrial DNA in an egg or embryo with healthy mitochondrial DNA from a donor

Question 13

gene therapy strategies aimed at modifying the disease cells

Answer 13

• Gene Augmentation Therapy
• Gene Silencing Therapy
• RNA Modulation Therapy
• Gene Editing

Question 14

gene therapy strategies aimed at killing harmful cells

Answer 14

• suicide gene therapy
• indirect cell killing

Question 15

explain how gene augmentation therapy works

Answer 15

• Identify the specific gene that is defective or missing in the patient’s cells
• A functional copy of the gene is introduced into the patient’s cells using a vector
• The introduced gene begins to produce a functional protein, restoring the normal cellular function that was impaired by the defective gene

Question 16

what type of disorders are more suited to these supplemental therapies

Answer 16

recessive disorders

Question 17

what is gene silencing therapy a suitable treatment for

Answer 17

infectious diseases
cancer
inherited disorders

Question 18

how does gene silencing work

Answer 18

Specific genes in our cells are turned off or reduced in their activity
RNA molecules attach to the mRNA, it prevents the gene from making proteins, essentially silencing its activity

Question 19

what is the aim of gene Editing

Answer 19

to correct the defect rather than silence or replace it

Question 20

how does gene editing work

Answer 20

Scientists design guide RNA which binds to the target DNA sequence.
It then makes a cut in the DNA strand.
The defective DNA strand is then replaced with a healthy copy.

Question 21

suicide gene therapy

Answer 21

It is a type of treatment that is used to kill specific cells, like cancer cells.
A harmless product is put into the cells.
These cells are given a medicine called a prodrug.
The gene changes the prodrug into a strong medicine that kills the cells.

Healthy cells are not killed

Question 22

indirect cell killing

Question 23

what is important when designing gene therapy strategies

Answer 23

• understanding the pathophysiology of disease
• understanding how a mutation leads to a disease
• determine which of the cells are suitable targets for effective therapy

Question 24

name the various methods for administrating genes

Answer 24

viral vectors
non- viral vectors
direct injection
ex vivo gene therapy
in viv gene therapy

Question 25

explain ex vivo gene therapy

Answer 25

cells are removed from the patient’s body, genetically modified outside the body to introduce the therapeutic gene, and then reinfused back into the patient.
This approach is often used for diseases affecting blood cells

Question 26

in vivo gene therapy

Answer 26

therapeutic genes are administered directly into the patient’s body, where they target specific tissues or organs. This approach is less invasive than ex vivo gene therapy but may require more efficient delivery systems to reach the target cells

Question 27

integration gene therapy

Answer 27

The delivered gene becomes a permanent part of the cell’s DNA allowing for long term expression of the therapeutic protein.

Question 28

non integration gene therapy

Answer 28

• The therapeutic gene remains separate from the host cell’s genome.
• The delivered gene exists as an episome.
• Every time the cell divides the mutation will be lost in one of the daughter cells and passed on in the other

Question 29

pros and cons of non viral methods of gene transfer

Answer 29

safe
but much lower level of expression/efficiency

Question 30

current treatment for Duchenne Muscular Dystrophy

Answer 30

• steroids to prolong ambulation
• ventilation to prolong life
  but still no specific therapy dealing with underlying cause