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Amino-Terminal Portion of CFTR Forms a Regulated Cl- Channel
UIRF #: 94040; Inventor: Dr. Michael Welsh and Dr. David Sheppard
Background:
Cystic fibrosis (CF) is the most fatal genetic disease that each year affects one in 2500 infants
born. The cystic fibrosis transmembrane conductance regulator (CFTR) protein supports the
body by regulating anion absorption between epithelial membranes. The CF disease is caused by
a mutation of the CFTR protein that effectively blocks ion exchange in and out of these cells
resulting in the cell’s inability to absorb water. A common symptom of CF is the formation of
excess mucus that promotes the ion/water preclusion as well as trapping unwanted bacteria
leading to chronic infections. The most prevalent CF mutation is the amino acid sequence
ΔF508, which has been found to cause an imbalance in chloride (Cl-) ion and water transport in
epithelial cells.
Technology Description:
To circumvent the adverse effects of ΔF508 researchers at the University of Iowa have
developed a method to modify the CFTR protein and provide an alternate pathway for regulating
the Cl- channel. The technology incorporates an artificial mutation, D836X, formed from the
amino-terminal portion of the CFTR protein. The D836X portion contained a nucleotide binding
domain, a membrane-spanning domain, and an R-domain, thus providing all the necessary
structures that necessitate a regulated Cl- channel. Furthermore, unlike a normal CFTR protein
phosphorylation is not necessary to open the Cl- channels even though results were shown that
activity increased with phosphorylation.
Technological Advantages:
BREAKTHROUGH IN DEVELOPING TREATMENTS FOR CYSTIC FIBROSIS: This
method provides potential applications to repair CFTR regulating properties and improve the ion
and water exchange in and out of cells.
Relevant Research:
David N. Sheppard, Lynda S. Ostedgaard, Devra P. Rich, and Michael J. Welsh; The AminoTerminal Portion of CFTR Forms a Regulated CL- Channel (1994); CELL, 76, 1091-98 available
at http://www.sciencedirect.com/science/article/pii/0092867494903859.
Patent Link:
Genes and Proteins for Treating Cystic Fibrosis: www.google.com/patents/US5958893.