RNA therapeutics in targeting G protein-coupled receptors: Recent advances and challenges

Wanjun Yuan; Xiangyang Shi; Leo Tsz On Lee

doi:10.1016/j.omtn.2024.102195

RNA therapeutics in targeting G protein-coupled receptors: Recent advances and challenges

Mol Ther Nucleic Acids. 2024 Apr 24;35(2):102195. doi: 10.1016/j.omtn.2024.102195. eCollection 2024 Jun 11.

Authors

Wanjun Yuan¹, Xiangyang Shi², Leo Tsz On Lee^{1

3}

Affiliations

¹ Cancer Centre, Faculty of Health Sciences, University of Macau, Taipa 999078, Macau, China.
² State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua University, Shanghai 201620, People's Republic of China.
³ Ministry of Education Frontiers Science Center for Precision Oncology, University of Macau, Taipa 999078, Macau, China.

Abstract

G protein-coupled receptors (GPCRs) are the major targets of existing drugs for a plethora of human diseases and dominate the pharmaceutical market. However, over 50% of the GPCRs remain undruggable. To pursue a breakthrough and overcome this situation, there is significant clinical research for developing RNA-based drugs specifically targeting GPCRs, but none has been approved so far. RNA therapeutics represent a unique and promising approach to selectively targeting previously undruggable targets, including undruggable GPCRs. However, the development of RNA therapeutics faces significant challenges in areas of RNA stability and efficient in vivo delivery. This review presents an overview of the advances in RNA therapeutics and the diverse types of nanoparticle RNA delivery systems. It also describes the potential applications of GPCR-targeted RNA drugs for various human diseases.

Keywords: G protein-coupled receptor; MT: Oligonucleotides: Therapies and Applications; RNA therapeutics; drug delivery; nanoparticles.

Publication types

Review