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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===Introduction=== | ===Introduction=== | ||
| - | * CF is a common lethal hereditary disorder caused by a mutation on CFTR on chromosome 7 | + | *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 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 | + | *The pathogenesis is clearly linked to the lack of CFTR in the respiratory epithelia |
| - | * Symptoms in first decade: | + | *Symptoms in first decade: |
| - | ** Thick mucus, colonization with infectious bacteria, and chronic airway inflammation | + | **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) | + | *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 | + | *Gene therapy must be carried out ''in vivo'', cannot be done ''ex vivo'' |
====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 |
| - | * Used CF patients who were in remarkably good health | + | *Used CF patients who were in remarkably good health |
| - | * 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 |
| - | * Results are short lived- at most 6 weeks | + | *Results are short lived-- at most 6 weeks |
| - | * Because of the immune response, will not be able to do multiple dosing | + | *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 | + | *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" | + | *"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" | + | *"To maintain chronic expression, adenovirus vectors will probably have to be administered repeatedly" |
| - | ** This is not possible with an immune response | + | **This is not possible with an immune response |
Current revision as of 19:30, 7 March 2010
Contents |
[edit] 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
[edit] 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 vivo
[edit] 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
[edit] 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
