Gene Transfer in Respiratory Epithelium Using Synthetic Vectors and Folic Acid Receptor

Abstract

Objective: Synthetic vectors may be an interesting alternative way compared with viral vectors. They are potentially less toxic and immunogenic. However, synthetic vectors use an aspecific electrostatic recognition. Cellular targeting is one of the major conditions for development of efficient synthetic vectors for gene therapy.

Method: A neutral colipid derived from archaebacteria with acid folic ligand was developed and associated with cationic lipid vector. Its efficiency was tested on human respiratory epithelium cell culture.

Results: Safe respiratory epithelium offer few targets for gene transfer. Indeed, using lectin for specific gene transfer is difficult because of numerous different oligosaccharides patterns. We studied the interest of folic acid receptor as a target for gene transfer. These receptors are sparsely represented on this epithelium but have a great affinity. We demonstrated a specific gene transfer using a competitive inhibition by free folic acid in media. For a healthy human respiratory cell line, this new vector is more efficient and less toxic than lipofectamin.

Conclusion: Despite a small presence on human respiratory epithelium, folic acid receptor is a pertinent target for nonviral gene transfer. This vector is to be tested on animals. Such a targeting will increase gene transfer because of low electrostatic disturbance. Neutral vector may decrease toxicity.