G-Quadruplex Linked DNA Guides Selective Transfection into Nucleolin-Overexpressing Cancer Cells.

Abstract

Gene therapy is a promising approach for treating tumors. Conventional approaches of DNA delivery depending on non-viral or viral vectors are unsatisfactory due to the concerns of biosafety and cell-targeting efficiency. The question how to deliver DNA into tumor cells efficiently and selectively is a major technological problem in tumor gene therapy. Here, we develop a vector-free gene transfer strategy to deliver genes effectively and selectively by taking advantage of targeting nucleolin. Nucleolin, a shuttle protein moving between cell membrane, cytoplasm and nuclei, is overexpressed in tumor cells. It has a natural ligand G-quadruplex (Gq). Gq-linked DNA (Gq-DNA) is likely to be internalized by ligand dependent uptake mechanisms independently of vectors after neutralizing negative charges of cell membrane by targeting nucleolin. This strategy is referred to as Gq-DNA transfection. Benefiting from its high affinity to nucleolin, Gq-DNA can be effectively delivered into nucleolin-positive tumor cells even nuclei. Gq-DNA transfection is characterized by low cytotoxicity, high efficiency, ease of synthesis, high stability in serum, direct access into nuclei, and specific nucleolin-positive tumor cell targeting.

• Authors: Mengxi Xiang, Yongkui Li, Jia Liu, Jie Shi, Yizhi Ge, Chen Peng, Yawen Bin, Zheng Wang, Lin Wang
• Journal: Pharmaceutics (Pharmaceutics) Vol. 14 Issue 10 (Oct 21 2022) ISSN: 1999-4923 [Print] Switzerland
• PMID: 36297681 (Publication Type: Journal Article)