1. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR 999078, China.
2. Macao Centre for Research and Development in Chinese Medicine, University of Macau, Macao SAR 999078, China.
3. Institute of Molecular Medicine (IMM), Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
4. Pharmacognosy Department, College of Pharmacy, Cairo University, Kasr el Aini St., Cairo 11562, Egypt.
* Mingju Shui and Zhejie Chen contributed equally to this work.
Gene therapy, an effective medical intervention strategy, is increasingly employed in basic research and clinical practice for promising and unique therapeutic effects for diseases treatment, such as cardiovascular disorders, cancer, neurological pathologies, infectious diseases, and wound healing. However, naked DNA/RNA is readily hydrolyzed by nucleic acid degrading enzymes in the extracellular environment and degraded by lysosomes during intracellular physiological conditions, thus gene transfer must cross complex cellular and tissue barriers to deliver genetic materials into targeted cells and drive efficient activation or inhibition of the proteins. At present, the lack of safe, highly efficient, and non-immunogenic drug carriers is the main drawback of gene therapy. Considering the dense hydroxyl groups on the benzene rings in natural polyphenols that exert a strong affinity to various nucleic acids via hydrogen bonding and hydrophobic interactions, polyphenol-based carriers are promising anchors for gene delivery in which polyphenols serve as the primary building blocks. In this review, the recent progress in polyphenol-assisted gene delivery was summarized, which provided an easily accessible reference for the design of future polyphenol-based gene delivery vectors. Nucleic acids discussed in this review include DNA, short interfering RNAs (siRNA), microRNA (miRNA), double-strand RNA (dsRNA), and messenger RNA (mRNA).
Keywords: gene therapy, polyphenols, nucleic acid, RNA, EGCG