Crystal's "Administration of an adenovirus containing the human CFTR cDNA to the respiratory tract of individuals with cystic fibrosis" 1994

From Biol557

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

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 vitro