Polyethylenimine shows properties of interest for cystic fibrosis gene therapy.

Before being considered for a cystic fibrosis (CF) gene therapy trial, any gene delivery agent must be able to show that it produces low levels of toxicity as well as being able to protect the DNA from nuclease degradation. Here we show that complexes of linear polyethylenimine (L-PEI) and DNA can repeatedly be administered to animals (up to 21 consecutive days) without eliciting an immune response against PEI/DNA particles or inducing toxic side effects due to accumulation of PEI in the lungs. However, the host response to the exogenous protein resulted in some decrease of expression. PEI-mediated transfection was unaffected by treatment of the complexes with DNase (frequently used to reduce the viscosity of lung secretions in CF patients). Taken together, these properties make L-PEI a valuable vector for gene therapy of CF.