Promising Use of Cyclodextrin-Based Non-Viral Vectors for Gene and Oligonucleotide Drugs

Abstract

Genes, short-hairpin RNA (shRNA), small-interfering RNA (siRNA), and decoy DNA can be principally used as tools for the treatment and prevention of many disorders, including but not limited to cancers, genetic disorders, and inherited diseases. This is accomplished by introducing exogenous nucleic acids into mammalian cells to modulate gene expression. However, direct use of such oligonucleotide drugs is hampered by several barriers, including their degradation by nucleases present in the blood and extracellular fluid, cell-membrane impermeability, and their retention in endosomes. To address this issue, the development of safe and effective delivery vectors has emerged as the main fundamental challenge for successful gene and oligonucleotide therapy. Due to the intrinsic risks associated with viral vectors, non-viral vectors have attracted increasing attention as gene and oligonucleotide carriers. We originally developed various cyclodextrin (CyD) conjugates with polyamidoamine (PAMAM) dendrimers as novel CyD-based polymers for the delivery of plasmid DNA, siRNA, shRNA, and decoy DNA. In this review, we describe the recent findings on PAMAM dendrimer conjugates using CyDs as carriers for gene, shRNA, siRNA, and decoy DNA delivery.