TRAIL-based gene delivery and therapeutic strategies

Authors: Hui-hai Zhong1,2, Hui-yuan Wang2, Jian Li1, Yong-zhuo Huang2
1 Shanghai University College of Sciences, Shanghai 200444, China
2 State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
Correspondence to: Yong-zhuo Huang:,
DOI: 10.1038/s41401-019-0287-8
Received: 22 May 2019
Accepted: 4 July 2019
Advance online: 23 August 2019


TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), also known as APO2L, belongs to the tumor necrosis factor family. By binding to the death receptor 4 (DR4) or DR5, TRAIL induces apoptosis of tumor cells without causing side toxicity in normal tissues. In recent years TRAIL-based therapy has attracted great attention for its promise of serving as a cancer drug candidate. However, the treatment efficacy of TRAIL protein was under expectation in the clinical trials because of the short half-life and the resistance of cancer cells. TRAIL gene transfection can produce a “bystander effect” of tumor cell killing and provide a potential solution to TRAIL-based cancer therapy. In this review we focus on TRAIL gene therapy and various design strategies of TRAIL DNA delivery including non-viral vectors and cell-based TRAIL therapy. In order to sensitize the tumor cells to TRAIL-induced apoptosis, combination therapy of TRAIL DNA with other drugs by the codelivery methods for yielding a synergistic antitumor efficacy is summarized. The opportunities and challenges of TRAIL-based gene delivery and therapy are discussed.
Keywords: TRAIL; gene delivery; gene therapy; DNA; drug delivery systems; non-viral vectors; cancer therapy

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