gene therapy Flashcards
what is gene therapy
Treatment of a disease by the transfer of genetic
material into a patient’s cells
what is a type of x linked disease
haemophilia
what is a type of autosomal recessive disease
sickle cell anaemia, cystic fibrosis
what is an autosomal dominant disease
Huntington’s disease
what diseases can be treated by gene therapy
cancers, cvd, infections, monogenic disease
disadvantages of gene therapy
limited to somatic cells
specificity
side effects
what is in vivo
put cells directly into a persons body
what is ex vivo
remove cells
change it
amplify it
put it back into patients body
what are types of viral vectors
Adenovirus (AV)
* Adeno-associated virus (AAV)
* Retrovirus (γ-retrovirus or lentivirus)
* Herpes simplex virus (HSV)
what is one advantage and disadvantage of viral vectors
High expression but
high immunogenicity
what are 3 gene therpay paradigms
Gene expression
Gene inhibition
Induction of cell death
what is gene expression (increase)
Provide or generate a functional gene product
what is gene inhibition (decrease)
Prevent expression of a gene product
what is induction of cell death
By apoptosis or cytotoxic drug
what paradigm is gene augmentation an example of?
gene expression (increase)
when is gene augmentation used
Diseases caused by loss of gene function
e.g. inherited monogenic recessive disorders
which paradigm is Generation of a functional gene
gene expression (increase)
when is generation of a functional gene used
Disease caused by a non-functional protein because the gene
contains a mutation
what mechanism are generation of a functional gene
Homologous recombination (HR)
Using gene editing (exogenous nucleases)
Exon skipping / exclusion
when is exon skipping used
Disease caused by a non-functional protein because an exon
* is duplicated
* is deleted
* contains a frame-shift mutation
* contains a nonsense mutation
what is the mechanism of exon skipping
Uses antisense oligonucleotides (ASO)
* Short synthetic single-stranded oligonucelotides
* Complementary to target mRNA
* Modified to prevent degradation by nucleases
when is reducing gene expression used
Dominant disorder e.g. Huntington’s disease
* Autoimmune diseases
* Cancer caused by protein overexpression
* Infections
what mechanisms can be used to reduce expression
Mechanisms?
* RNAi
* Antisense oligonucleotides
* Ribozymes
* Decoy strategy
when is cell death used
Cancers
* Infections
