Gene Therapy Flashcards
Definition of gene therapy
Use of recombinant genetic material (DNA, RNA, hybrid molecules) under different forms or pharmaceutical preparations as a therapeutic agent
Definition of non integrating
Transgene not inserted into host DNA so it is not constantly expressed
Definition of integrating
Transgene inserted into host DNA so it is constantly expressed
What is gene therapy
What is legal
Recombinant genetic material (DNA, RNA, hybrid molecules) under different forms or pharmaceutical preparations as a therapeutic agent
Only somatic gene therapy is legal
Germline gene manipulation is illegal => designer babies
What are the 2 gene therapy delivery protocols
In vivo
-viruses containing recombinant genetic material is injected into the body part affected
Ex vivo
- haematopoietic target cells isolated and infected with RGM
- recombinant SC expanded and reinfused
What are the 3 components of gene therapy protocol
What is the most ideal cell target
Target tissue
- Accessible
- Manipulable
Efficient gene delivery
- Viral vector
- Non viral vector
Transcriptional control
- Sufficiently high
- Sustained
Pluripotent
Self regenerating stem cells from patient being treated
What are the 4 main viral gene therapy vectors
What are their fates post delivery
Adenovirus, non integrating
Adeno associated, non integrating
Retrovirus, integrating
Lentivirus, integrating
Describe the use of retro and lentiviruses
- Remove disease causing gene
- Insert plasmids that encode for the gene and proteins that can make the virus
Does not have genes for further replication
How is transcription regulated
- transient
- long term
Transient
- for acquired diseases
- use non replicating viruses
- repeated administration
- target tissue specific promotors/enhancers
Long term
- for inherited and acquired diseases
- stable integration of transgenic material
- negate chromatin interference of expression with LCRs
What should you watch out for when using retroviruses
Only transduce dividing cells
Preferential integration near/in genes being actively transcribed in targeted cells at time of transduction
-if uncontrolled => insertion into genes that control cell
Need to stabilise promoter for transgene
-if not done => promoter methylated and silenced
Describe current gene therapy
Viral vectors can successfully used but must be designed to be more reliable
Gene therapy medicines are currently being used
What are the potential developments in gene therapy
In vivo targeted gene delivery systems
Efficient non viral vectors
Minimise risks such as insertional mutagenics
