Gene therapy Flashcards
What is gene replacement?
Replace faulty genes with normal ones, corrects inherited genetic errors.
Adding back or restoring a missing function.
Monogenic diseases e.g cystic fibrosis, haemophilia, X-SCID.
What is gene addition?
Deliver genes to provide a new function. Polygenic diseases such as cancer. Add a new ‘gene’:
Gene immunotherapy for cancer.
GDEPT.
What is GDEPT? [5]
- Virus encoding suicide enzyme enters target cell via transduction.
- Suicide gene expression occurs.
- Suicide enzyme converts non-toxic prodrug into active toxic drug,
- Death of transduced tumour cells.
- Death of neighbouring cells through bystander effects.
(HSV, Transgene thymidine kinase)
What is the perfect vector for gene therapy? [5]
- Easily and cheaply produced.
- Targeted
- High Gene expression
- Regulation of gene expression
- No adverse/pathogenic effects.
What non-viral vectors exist? [5]
- Naked DNA
- Lipoplexes (liposomes/DNA)
- Polyplexes (polymer/DNA)
- Lipopolyplexes (liposome/polymer/DNA)
- Carboplexes (carbon nanotudes/DNA)
What are lipoplexes?
Liposomes and DNA
What are polyplexes?
Polymers and DNA
What are lipopolyplexes?
Liposome/Polymer/DNA
What are carboplexes?
Carbon nanotubes and DNA
What viral vectors exist?
DNA viruses (adenovirus, adeno-associated, HSV) RNA viruses (lentivirus, retrovirus.
What DNA virus vectors exist?
Adenovirus, Adeno-associated virus, HSV.
What RNA virus vectors exist?
Lentivirus, Retrovirus
How do RNA viruses function as vectors?
Integrate into host DNA for transgene expression.
Adv: long-term expression of therapeutic gene.
Dis: cancer, disruption of cell cycle regulation.
What are the advantages and disadvantages of RNA virus vectors?
Adv: long-term expression of therapeutic genes.
Dis: cancer, disruption to cell cycle regulation.
How do DNA viruses function as vectors?
DNA expression without integration into host genome.
What are the advantages of DNA virus vector use?
In-vivo.
Dis: short term expression as no integration. Repeated administration is needed. Can provoke immune reaction.
What are some licenced gene therapy products?
- Gendicine
- H101
- Glybera
What does Gendicine treat?
Replication deficient adenovirus carrying p53.
What does H101 treat?
Recombinant oncolytic Adenovirus targeting p53-deficient tumour cells.
What does Glybera treat?
Alipogene tiparvovac - Adeno-associated virus delivering the lipoprotein lipase gene.
What does Ex Vivo gene therapy involve?
- Remove faulty cells from patient.
- Transfect cells with therapeutic gene outside the body.
- Return cells to the patient.
What is In Vivo gene therapy?
Inject the DNA liposome or Recombinant virus etc into the body. Which it then infects cells of the body,
What regulations govern the handling of gene therapy in viral vectors?
- GMO (Contained Use) Regs 2014, HSE.
2. GMO (Deliberate Release) Regs 2002, DEFRA.
What do the GMO (Contained Use) Regs 2014, HSE stipulate?
All possible barriers (physical, biological or chemical) are in place to limit contact of the GMOs with humans and the environment,
What do the GMO (Deliberate Release) Regs 2002, DEFRA stipulate?
All appropriate measures are taken to avoid damage to the environment from the escape or release from human control of GMOs.
What additional regulations apply to gene therapy clinical trials?
The protection of the patient must be the first priority.
Gene Therapy Advisory Committee (GTAC). Est. 1993, Department of Health. UK National research ethics committee (REC) for gene therapy.
What is the GTAC?
Gene Therapy Advisory Committee (GTAC). Est. 1993, Department of Health. National research ethics committee (REC) for gene therapy.
