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Updated: Jul 17, 2025

Electroporation-Mediated Delivery of Cas9 Ribonucleoproteins and mRNA into Freshly Isolated Primary Mouse Hepatocytes
Published on: June 2, 2022
RNAi therapies: Expanding applications for extrahepatic diseases and overcoming delivery challenges
Jong Won Lee1, Man Kyu Shim2, Hyosuk Kim2
1KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 02841, Republic of Korea; Medicinal Materials Research Center, Biomedical Research Division, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea.
Abstract:
The era of RNA medicine has become a reality with the success of messenger RNA (mRNA) vaccines against COVID-19 and the approval of several RNA interference (RNAi) agents in recent years. Particularly, therapeutics based on RNAi offer the promise of targeting intractable and previously undruggable disease genes. Recent advances have focused in developing delivery systems to enhance the poor cellular uptake and insufficient pharmacokinetic properties of RNAi therapeutics and thereby improve its efficacy and safety. However, such approach has been mainly achieved via lipid nanoparticles (LNPs) or chemical conjugation with N-Acetylgalactosamine (GalNAc), thus current RNAi therapy has been limited to liver diseases, most likely to encounter liver-targeting limitations. Hence, there is a huge unmet medical need for intense evolution of RNAi therapeutics delivery systems to target extrahepatic tissues and ultimately extend their indications for treating various intractable diseases. In this review, challenges of delivering RNAi therapeutics to tumors and major organs are discussed, as well as their transition to clinical trials. This review also highlights innovative and promising preclinical RNAi-based delivery platforms for the treatment of extrahepatic diseases.
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