The study focuses on the efficacy and biocompatibility of GL-67:DOPE (1:2) liposomes in gene delivery applications, with a particular emphasis on their utilization in both preclinical and clinical trials. GL-67, a cationic lipid with T-shaped head groups, has been identified as exceptionally efficient for gene transfer to cells in culture and murine lungs, surpassing the gene delivery capabilities of its analogs, including DC-Chol. This superior performance is attributed to GL-67's unique structural properties, which include a carbamate-based linkage offering stability at neutral pH yet allowing for acid-catalyzed hydrolysis under specific conditions. The liposomes formulated from GL-67 have demonstrated significant promise in gene therapy, illustrated by their central role in a phase I clinical trial for cystic fibrosis. In this trial, patients received GL-67:DOPE liposome-mediated CFTR gene delivery, which successfully transferred CFTR cDNA to airway epithelia and partially corrected the chloride transport defect characteristic of cystic fibrosis. These findings underscore the potential of GL-67:DOPE liposomes as a non-viral gene delivery system that combines high transfection efficiency with minimal toxicity, highlighting their relevance in advancing gene therapy applications.
Zhi, D., Bai, Y., et al. A review on cationic lipids with different linkers for gene delivery. Advances in colloid and interface science. 2018, 253: 117-140.
For Research Use Only. Not For Clinical Use