Elucidating Glycopolycation Structure-Function Relationships For Improved Gene Therapy

Abstract

The gene therapy field is devoted to treating disease by adding, altering, or inhibiting gene expression. This type of therapy holds great promise for the treatment and even cure of monogenic diseases such as cystic fibrosis, Duchenne muscular dystrophy, hemophilia A and B, and epidermolysis bullosa. To produce therapeutic effect, nucleic acids must be delivered and expressed in cells of interest. Deoxyribonucleic acids (DNA) and ribonucleic acids (RNA) in many forms can be delivered using viral or non-viral vehicles. Viral vectors provide efficient DNA delivery; however, packaging limitations and occasional safety issues such as immune responses are major issues. In contrast, non-viral vectors are cheaper and easier to mass produce and can package any length of nucleic acid; however, non-viral vectors struggle to deliver genetic cargo at therapeutically beneficial levels. Polymers with the ability to condense and protect genetic material make promising non-viral vectors. They are relatively easy to produce compared to viral vehicles, can safely package various plasmid sizes, and have shown significant uptake in a wide variety of human cell lines. Cationic polymers complex with the negatively charged phosphodiester backbone of DNA or RNA, forming inter-polyelectrolyte complexes termed polyplexes. Herein, we explore using experiments in vitro, ex vivo, and in vivo to probe the structure-function relationships dictating polyplex gene delivery and other glycomaterial applications.