Glatiramer Acetate (Copaxone®) is a Promising Gene Delivery Vector.

Glatiramer Acetate (Copaxone®) is a Promising Gene Delivery Vector.

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.

Concepts Keywords
Acetate Polylysine
Active Ingredient Transfection
Alanine Glatiramer acetate
Amino Acids Life sciences
Calcium Applied genetics
Cervical Biotechnology
Copaxone Molecular biology
Cytotoxicity MS
DNA Gene delivery
Genetic Branches of biology
Genetic Material
Glutamic Acid
HeLa
K9
Lung
Lysine
Mixing
Molecular Weight
Multiple Sclerosis
Myelin
Nanoparticle
Nanoparticles
PDNA
Plasmid
Polyelectrolyte
Polypeptides
Transfect
Transfection
Tyrosine

Semantics

Type Source Name
drug DRUGBANK Calcium
gene UNIPROT C1QL3
disease DOID cervical cancer
disease MESH cervical cancer
disease DOID lung cancer
disease MESH lung cancer
pathway BSID Gene Expression
gene UNIPROT LITAF
drug DRUGBANK L-Lysine
drug DRUGBANK L-Tyrosine
drug DRUGBANK Glutamic Acid
drug DRUGBANK L-Alanine
drug DRUGBANK Amino acids
gene UNIPROT MBP
gene UNIPROT PRG2
gene UNIPROT MBL2
disease DOID multiple sclerosis
disease MESH multiple sclerosis
drug DRUGBANK Glatiramer

Original Article

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