Efficient and persistent gene transfer of AAV-CFTR in maxillary sinus

Cystic fibrosis is a common, lethal, genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), and it is an attractive target for gene therapy. Adeno-associated virus (AAV) is a naturally replication-deficient single-stranded DNA parvovirus. Preclinical studies showed that CFTR transcripts and protein can be detected up to 6 months after transduction with an AAV-CFTR vector, 1 Flotte TR Afione SA Conrad C et al. Stable in vivo expression of the cystic fibrosis transmembrane conductance regulator with an adeno-associated virus vector. Proc Natl Acad Sci USA. 1993; 90: 10613-10617 Crossref PubMed Scopus (443) Google Scholar with no pathogenicity, 2 Conrad CK Allen SS Afione SA et al. Safety of single-dose administration of an adeno-associated virus (AAV)-CFTR vector in the primate lung. Gene Ther. 1996; 3: 658-668 PubMed Google Scholar suggesting that AAV performs well as a gene transfer vehicle for CFTR. The maxillary sinuses are attractive for evaluating new treatments of cystic fibrosis because they have ion-transport systems and microbiology similar to those of the lower respiratory tract. 3 Moss RB King VV Management of sinusitis in cystic fibrosis by endoscopic surgery and serial antimicrobial lavage: reduction in recurrence requiring surgery. Arch Otolaryngol Head Neck Surg. 1995; 121: 566-572 Crossref PubMed Scopus (121) Google Scholar , 4 Wine JJ King VV Lewiston NJ Method for rapid evaluation of topically applied agents to cystic fibrosis airways. Am J Physiol. 1991; 261: L218-L221 PubMed Google Scholar Recurrence of maxillary sinusitis may prove to be a surrogate for infectious exacerbations characteristic of cystic fibrosis lung disease.