The objective of the proposed research is the formulation of effective therapeutic replacement surfactant to be used in the treatment of infant Respiratory Distress Syndrome (RDS), caused by inadequate levels of lung surfactant at birth. Pulmonary surfactant is a lipid-protein complex, in which a group of very hydrophobic surfactant proteins promotes the surface activity of the phospholipid components. Treatment of RDS using natural lung surfactant supplements appears effective, but these formulations contain either relatively impure preparations of animal surfactant proteins, or very scarce natural human proteins. We have isolated the genes for the two hydrophobic human surfactant proteins. Here we outline our plan for expressing and purifying these proteins recombinantly, then testing them in vitro and in vivo after formulation with phospholipids. The application of recombinant DNA techniques to express the isolated genes for the human surfactant proteins should provide unlimited quantities of replacement surfactant formulated with synthetic phospholipids and pure recombinant human protein.
