Publication date: Mar 13, 2019
Glatiramer acetate (GA), the active ingredient of Copaxone(R), consists of random polypeptides used to treat multiple sclerosis (MS). GA was originally designed to emulate myelin basic protein (MBP) and contains the four amino acids: alanine, glutamic acid, tyrosine, and lysine. We found that GA can complex, condense, and transfect plasmid DNA. Mixing the positively-charged GA and the negatively-charged genetic material at the correct proportions produced small, stable, and highly positively-charged nanoparticles. This simple GA-pDNA formulation produced high levels of gene expression and negligible cytotoxicity in A549 lung cancer cells and HeLa cervical cancer cells. In addition, we compared the nanoparticle properties, transfection efficiency, and cytotoxicity of K100-pDNA (high-molecular-weight polylysine) and K9-pDNA (low-molecular-weight polylysine) nanoparticles to GA-pDNA nanoparticles. We also studied the effect of calcium, which was previously reported to reduce the size and enhance gene expression resulting from similar polyelectrolyte complexes. Adding calcium did not reduce particle size, nor improve transfection efficiency of GA-pDNA nanoparticles as it did for polylysine-pDNA nanoparticles. GA-pDNA nanoparticles may be prepared by mixing a genetic payload with approved GA therapeutics (e.g., Copaxone(R)), thus offering intriguing possibilities for translational gene therapy studies.
Alhakamy, N.A. and Berkland, C.J. Glatiramer Acetate (Copaxone(R)) is a Promising Gene Delivery Vector. 17505. 2019 Mol Pharm.