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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* One approach to prevent respiratory manifestations of CFTR is gene therapy (talked about in abstract) | * 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 | * 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 foru human gene therapy trails 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 heatlh | ||
| + | * 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 | ||
Revision as of 02:25, 4 March 2010
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 foru human gene therapy trails 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 heatlh
- 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
