Crystal's "Administration of an adenovirus containing the human CFTR cDNA to the respiratory tract of individuals with cystic fibrosis" 1994
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* Gene therapy must be carried out in vivo, cannot be done ex vitro | * Gene therapy must be carried out in vivo, cannot be done ex vitro | ||
| - | I also decided to add in the notes I took in class just for completeness | + | ====I also decided to add in the notes I took in class just for completeness==== |
* One of the four human gene therapy trials approved and initiated at the same time | * One of the four human gene therapy trials approved and initiated at the same time | ||
* Based on the results of this trial, the others were halted | * Based on the results of this trial, the others were halted | ||
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* Did multiple dosing to find effecting concentration | * Did multiple dosing to find effecting concentration | ||
| - | Results in the human study: | + | ====Results in the human study:==== |
* Treatment evoked an immune response | * Treatment evoked an immune response | ||
* Inflammation accompanied the immune response | * Inflammation accompanied the immune response | ||
Revision as of 14:14, 5 March 2010
Contents |
Abstract
- They administered a recombinant adenovirus vector (AdCFTR) containing the normal human CFTR cDNA into the nasal and bronchial epithelium of 4 individuals with CF.
- They found the vector expresses the CFTR cDNA in the respiratory epithelium in vivo.
- At 2x109 pfu there was no recombination, complementation, shedding of the vector, or rise in antibody titres. Although, there was a transient and systemic pulmonary syndrome observed (possibly mediated by IL-6)
- They saw no long term effects
Introduction
- CF is a common lethal hereditary disorder caused by a mutation on CFTR on chromosome 7
- The disorder is characterized by airway and gastrointestinal disease, the lung manifestations dominate
- The pathogenesis is clearly linked to the lack of CFTR in the respiratory epithelia
- Symptoms in first decade:
- Thick mucus, colonization with infectious bacteria, and chronic airway inflammation
- One approach to prevent respiratory manifestations of CFTR is gene therapy (talked about in abstract)
- Gene therapy must be carried out in vivo, cannot be done ex vitro
I also decided to add in the notes I took in class just for completeness
- One of the four human gene therapy trials approved and initiated at the same time
- Based on the results of this trial, the others were halted
- Used CF patients who were in remarkably good health
- Did multiple dosing to find effecting concentration
Results in the human study:
- Treatment evoked an immune response
- Inflammation accompanied the immune response
- Results are short lived- at most 6 weeks
- Because of the immune response, will not be able to do multiple dosing
- Very inefficient transfer of gene of interest- will do nothing to correct the defect
- "Correction of the CF phenotype of the airway epithelium might be achieved with this strategy"
- "To maintain chronic expression, adenovirus vectors will probably have to be administered repeatedly"
- This is not possible with an immune response
