A 2ND DOSE OF A CFTR CDNA-LIPOSOME COMPLEX IS AS EFFECTIVE AS THE FIRST DOSE IN RESTORING CAMP-DEPENDENT CHLORIDE SECRETION TO NULL CF MICETRACHEA

Phase I clinical trials have provided encouraging data suggesting that gene transfer could provide a treatment for cystic fibrosis (CF). How ever, for all the current viral and nonviral vectors used to deliver t he cystic fibrosis transmembrane conductance regulator (CFTR) gene, th e duration of CFTR expression is limited, necessitating a repeat dosin g regimen to provide a long-term treatment This study was performed to determine whether a second delivery of a CFTR cDNA-liposome complex c ould result in a similar level of functional CFTR expression observed after a single delivery and to assess whether the deliveries produced adverse inflammatory responses. CFTR functional expression was assesse d by short circuit current measurements of tracheas taken from CF null mice (Cftr(tm1Cam)) treated with a CFTR cDNA-liposome complex in the upper airways. Mice receiving two deliveries of this complex, the seco nd after the response to the first had declined, showed cAMP-stimulate d chloride currents which were not significantly different from normal tracheas or tissues assayed after a single dose of the complex. This double treatment was well tolerated with no discernible inflammation o f lung tissue.