These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Ability of a chimeric cAMP-responsive promoter to confer pharmacologic control of CFTR cDNA expression and cAMP-mediated Cl- secretion.
    Author: Suzuki M, Singh RN, Crystal RG.
    Journal: Gene Ther; 1997 Nov; 4(11):1195-201. PubMed ID: 9425443.
    Abstract:
    Based on the theoretical concern that chronic over-expression of the exogenous CFTR protein could be associated with adverse effects following gene transfer, we have constructed a replication-deficient adenovirus (Ad) vector containing the normal human CFTR cDNA controlled by a chimeric, cAMP-regulatable promoter responsive to agents that elevate intracellular cAMP levels. Studies with the IB3 human CF-derived respiratory epithelial line as a model target for CF gene therapy and forskolin to elevate cAMP levels demonstrated that following infection with the AdCF126(CRE8) CFTR vector, there was a marked increase in CFTR mRNA levels after forskolin addition. There was an associated correction of cAMP-mediated Cl- secretion that could be further increased with additional forskolin. cAMP-mediated Cl- secretion was corrected with vector doses as low as 0.2 MOI, a dose that can be achieved in vivo in humans. These observations suggest the feasibility of using a regulatable promoter for gene therapy for CF, with the promoter and gene product stimulated by the same class of pharmacologic agents.
    [Abstract] [Full Text] [Related] [New Search]