12. Gene Therapy Flashcards
what is gene therapy
A medical approach that treats or prevents disease by correcting the underlying genetic defect
SCID
commonly referred to as bubble boy disease
SCID gene therapy trial
in Paris
treated 11 boys
- 9 cured
- 4 of these developed leukemia 3-6 years later
- 1 died
- FDA paused trials
what was the first gene therapy approved in Europe
- treats ultra rare Lipoprotein Lipase Deficiency
- cost: over 1mil per patient
- drug withdrawn in 2017 due to high costs and rarity of patient
Spinal Muscular Atrophy
- SMN1 protein is necessary for normal motor neuron function
- mutation of SMN1 gene leads to irreversible deterioration of motor neurons in spinal cord
Zolgensma
- 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
Dystrophic Epidermolysis Bullosa
a rare genetic skin disorder where the skin becomes fragile and prone to blistering
Luxturna
a gene therapy medication used to treat inherited retinal diseases caused by mutations in the RPE65 gene.
what is the ultimate aim of gene therapy
to change gene expression in relevant cells so that disease symptoms are cured or reduced without any adverse effects
somatic gene therapy
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
germline gene therapy
modifying genetic material of reproductive cells with the goal of passing the genetic modifications onto future generations
mitochondrial DNA replacement therapy
replacing defective mitochondrial DNA in an egg or embryo with healthy mitochondrial DNA from a donor
gene therapy strategies aimed at modifying the disease cells
- Gene Augmentation Therapy
- Gene Silencing Therapy
- RNA Modulation Therapy
- Gene Editing
gene therapy strategies aimed at killing harmful cells
- suicide gene therapy
- indirect cell killing
explain how gene augmentation therapy works
- 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
what type of disorders are more suited to these supplemental therapies
recessive disorders
what is gene silencing therapy a suitable treatment for
infectious diseases
cancer
inherited disorders
how does gene silencing work
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
what is the aim of gene Editing
to correct the defect rather than silence or replace it
how does gene editing work
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.
suicide gene therapy
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
indirect cell killing
what is important when designing gene therapy strategies
- understanding the pathophysiology of disease
- understanding how a mutation leads to a disease
- determine which of the cells are suitable targets for effective therapy
name the various methods for administrating genes
viral vectors
non- viral vectors
direct injection
ex vivo gene therapy
in viv gene therapy
explain ex vivo gene therapy
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
in vivo gene therapy
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
integration gene therapy
The delivered gene becomes a permanent part of the cell’s DNA allowing for long term expression of the therapeutic protein.
non integration gene therapy
- 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
pros and cons of non viral methods of gene transfer
safe
but much lower level of expression/efficiency
current treatment for Duchenne Muscular Dystrophy
- steroids to prolong ambulation
- ventilation to prolong life
but still no specific therapy dealing with underlying cause
