Innovative trends in RNA interference drugs: a comprehensive patent analysis

doi:10.5246/jcps.2025.08.052

Abstract

Abstract:

Nucleic acid drugs represent the third wave of innovation in drug research and development, succeeding small-molecule and antibody drugs. These drugs, particularly RNA interference (RNAi) therapies, have become a pivotal focus in the pharmaceutical industry. RNAi drugs are extensively utilized in the treatment of chronic and rare diseases due to their exceptional gene-silencing efficiency, manageable side effects, and straightforward synthesis process. This study undertook a thorough analysis of the global landscape of RNAi drug patents, highlighting the latest technological advancements and trends. We meticulously identified and cataloged the key technologies that dominated this patent landscape. The goal was to provide valuable insights and references for researchers involved in the development of RNAi drugs within the domestic pharmaceutical sector.

Key words: Nucleic acid drugs, RNA interference (RNAi) drugs, siRNA, Patent analysis

Supporting:

Xing Li, Lu Ma, Yali Zhao, Xiaoxia Zhang, Zijia Li. Innovative trends in RNA interference drugs: a comprehensive patent analysis[J]. Journal of Chinese Pharmaceutical Sciences, 2025, 34(8): 701-714.

Figures/Tables 8

References 10

[1]	Li, Q.; Chen, R.; Hu, P. Recent advances in pharmacokinetic characteristics and physiological pharmacokinetic modeling of small interfering RNA (siRNA) drugs. Acta Pharmaceutica Sinica. 2022, 57, 3146–3156.
[2]	Alshaer, W.; Zureigat, H.; Al Karaki, A.; Al-Kadash, A.; Gharaibeh, L.; Hatmal, M.M.; Aljabali, A.A.A.; Awidi, A. siRNA: Mechanism of action, challenges, and therapeutic approaches. Eur. J. Pharmacol. 2021, 905, 174178.
[3]	Zhu, L.F.; Wang, Z.J. A nalysis of Global Gene Therapy Drug Development Status. Prog. Pharm. Sci. 2022, 46, 325–338.
[4]	Guan, R.B.; Li, H.C.; Miao, X.X. Commercialization status and existing problems of RNA biopesticides. Scientia Agricultura Sinica. 2022, 55, 2949–2960.
[5]	John, M. Reflections on Alylam. Nat. Biotechnol. 2022, 40, 641–650.
[6]	Paunovska, K.; Loughrey, D.; Dahlman, J.E. Drug delivery systems for RNA therapeutics. Nat. Rev. Genet. 2022, 23, 265–280.
[7]	Ge, J.; Chen, L.F.; Nie, X.Y.; Chen, J. Analysis of patent development status of lipid nanoparticle delivery system form RNA vaccines. J. Chin. Pharm. Sci. 2023, 32, 112–121.
[8]	Zhang, L.; Liang, Y.Y.; Liang, G.H.; Tian, Z.L.; Zhang, Y.; Liu, Z.H.; Ji, X.Y. The therapeutic prospects of N-acetylgalactosamine-siRNA conjugates. Front. Pharmacol. 2022, 13, 1090237.
[9]	Brown, C.R.; Gupta, S.; Qin, J.E.; Racie, T.; He, G.; Lentini, S.; Malone, R.; Yu, M.; Matsuda, S.; Shulga-Morskaya, S.; Nair, A.V.; Theile, C.S.; Schmidt, K.; Shahraz, A.; Goel, V.; Parmar, R.G.; Zlatev, I.; Schlegel, M.K.; Nair, J.K.; Jayaraman, M.; Manoharan, M.; Brown, D.; Maier, M.A.; Jadhav, V. Investigating the pharmacodynamic durability of GalNAc-siRNA conjugates. Nucleic Acids Res. 2020, 48, 11827–11844.
[10]	Sun, B.; Lin, J.J.; Wang, S.S.; Sun, S.G. siRNAs and microRNAs are used for antiviral research progress. Chin. Med. Biotechnol. 2021, 16, 51–57.

[1]	Shuwen Tong, Xianrong Qi. A comprehensive comparative analysis of transfection reagents for siRNA delivery [J]. Journal of Chinese Pharmaceutical Sciences, 2024, 33(1): 26-34.
[2]	Jia Ge, Longfei Chen, Xiaoyan Nie, Jing Chen. Analysis of patent development status of lipid nanoparticle delivery system for mRNA vaccines [J]. Journal of Chinese Pharmaceutical Sciences, 2023, 32(2): 112-121.
[3]	Kaisen Li, Rudong Wang, Yiwei Peng, Dawen Dong, Xianrong Qi. Riboflavin-modified lipo-polyplexes co-delivering CXCR4 siRNA and doxorubicin for treatment of highly metastatic cancer [J]. Journal of Chinese Pharmaceutical Sciences, 2021, 30(3): 189-205.
[4]	Kexiang Gao, Xiaoyan Liu, Yuanjun Zhu, Ye Liu, Yinye Wang. The influence of B55γ on the neuroprotective effect of W026B in t-MCAO mice [J]. Journal of Chinese Pharmaceutical Sciences, 2020, 29(10): 711-718.
[5]	Piaopiao Li, Yi Yan, Haitao Zhang, Ru Wang, Huhu Han, Jiancheng Wang. Treatment of cervical cancer by siRNA-loaded chitosan-coated calcium phosphate nanoparticles [J]. Journal of Chinese Pharmaceutical Sciences, 2018, 27(8): 517-529.
[6]	Yi Yan, Shihe Cui, Jing Sun, Piaopiao Li, Haitao Zhang, Jiancheng Wang. Novel cationic lipid with reduction-responsive cleavable hydrophobic tail for siRNA delivery [J]. Journal of Chinese Pharmaceutical Sciences, 2018, 27(6): 383-396.
[7]	Mengyi Yang, Jing Sun, Chao Wang, Yanfen Zhang, Lihe Zhang, Zhenjun Yang. Transfection of 3′,3′′-bis-peptide-siRNA conjugate by cationic lipoplexes mixed with a neutral cytosin-1-yl-lipid [J]. Journal of Chinese Pharmaceutical Sciences, 2017, 26(10): 719-726.
[8]	Chong Qiu, Shihe Cui, Jing Sun, Jiancheng Wang. In vitro comparative evaluation of three CLD/siRNA nanoplexes prepared by different processes [J]. Journal of Chinese Pharmaceutical Sciences, 2016, 25(9): 660-668.
[9]	Yiping Diao, Jing Sun, Mengyi Yang, Bo Xu, Lihe Zhang, Zhenjun Yang. Evaluation of the intracellular trafficking of siRNAs in A375 cells by confocal laser scanning microscopy [J]. Journal of Chinese Pharmaceutical Sciences, 2016, 25(12): 859-868.
[10]	Lang Zou, Ye Huang, Xiaofeng Wang, Yuan Ma, Yang Liu, Zhu Guan, Lihe Zhang, Zhenjun Yang. Serum stability enhancement of siRNA caused by peptide conjugation at 3'-terminus of sense strand [J]. Journal of Chinese Pharmaceutical Sciences, 2014, 23(4): 215-219.
[11]	Jingquan Li, Zhenzhen Yang, Tingting Meng, Xianrong Qi . The use of cationic liposomes to co-deliver docetaxel and siRNA for targeted therapy of hepatocellular carcinoma [J]. Journal of Chinese Pharmaceutical Sciences, 2014, 23(10): 667-673.
[12]	Yating Li, Yi Zheng, Delin Pan, Bo Xu, Yun Wu^*, Zhenjun Yang, Lihe Zhang . Development of a high-content screening method to evaluate the cellular population-based biological activity of new siRNA delivering reagent [J]. Journal of Chinese Pharmaceutical Sciences, 2013, 22(6): 467-474.
[13]	Ye Huang, Xiaofeng Wang, Zhenjun Yang^*, Lihe Zhang . Modification of oligonucleotides by isonucleosides incorporation and peptides conjugation [J]. , 2012, 21(6): 499-508.
[14]	Yue Chen, Xiao-Feng Wang, Ye Huang, Li-He Zhang, Zhen-Jun Yang^* . Chemically modified siRNAs and their conjugates [J]. , 2012, 21(1): 5-20.
[15]	Ting Yang, Zhi-Xia Zhao, Zhen-Zhong Xu, En-Yu Zhao, Xiao-Yan Liu, Cheng-Jun Chen, Jian-Cheng Wang^*, Qiang Zhang . Tumor-targeted delivery of siRNA by surface-modified LPC nanoparticles [J]. , 2011, 20(6): 590-596.