Gene therapy is potentially a viable treatment for chemotherapy-resistant cancers. However, gene therapy safety and efficacy are still not optimum. The main challenges to gene therapy have been cytotoxicity, rapid degradation, and low cellular up take. One of the most promising non-viral vectors used in gene therapy, polyethyleneimine (PEI) have been used widely. PEI has a high charge density that condenses the nucleic acids, protects them against nucleases, solving the challenge of rapid degradation. This protection is further enhanced by liposomal coating. The 22kDa lPEI has two key features that make it suitable for gene therapy: it is fully deacylated and lacks primary amines. The two elements, respectively, make it have higher transfection efficiency and less cytotoxicity than the branched chain variants.
Researchers led by Professor Udo Bakowsky at the University of Marburg in Germany developed a novel safer and more efficient vehicle . The research work is now published in journal , Colloids and Surfaces B: Biointerfaces. The researchers encapsulated linear PEI ( lPEI) complexed with nucleic acids within (1,2-Dioleoyl-sn-glycerol-3-phosphoethanolamine) (DOPE), (Dipalmitoylphosphatidylcholine) (DPPC), and cholesterol (DDC) liposomes to form lipopolyplexes . The liposomes, owing to their negative surface charge, shielded the positively charged PEI. thereby reducing its cytotoxicity dramatically.
The research was intended to help in improving the efficacy of gene therapy as a cancer treatment modality.
The results showed that the lipopolyplexes had superior features as a vehicle for transfecting cancer cells. The lipopolyplexes also showed good biocompatible and haemocompatible properties and were stable at physiological heparin concentrations.
The findings by the University of Marburg scientists will potentially improve the outcomes in the treatment of chemotherapy-resistant cancers, especially where gene therapy has failed because of cytotoxicity and adverse immune reactions. The gene delivery vehicles had the following advantages: better integrity and stability of the polyplexes; the liposomal layer around the polyplexes shielding against heparin and competing polyanions; ability to cross the plasma membrane.
The researchers propose the application of these lipopolyplexes for in vivo gene therapy. Its efficacy has been proven in vitro, and only needs a clinical trial on patients to bring on board other parameters that need consideration before its use in therapy.
Pinnapireddy, Shashank Reddy, et al. “Composite liposome-PEI/nucleic acid lipopolyplexes for safe and efficient gene delivery and gene knockdown.” Colloids and Surfaces B: Biointerfaces 158.2017 (2017): 93-101.