Advanced Nanotechnology-Based Nucleic Acid Medicines

Overview

Journal Pharmaceutics

Publisher MDPI

Date 2024 Nov 27

PMID 39598491

Authors

Noriko Miyamoto

Mina Sakuragi

Yukio Kitade

Affiliations

Soon will be listed here.

Abstract

Nucleic acid medicines are a highly attractive modality that act in a sequence-specific manner on target molecules. To date, 21 such products have been approved by the Food and Drug Administration. However, the development of nucleic acid medicines continues to face various challenges, including tissue and cell targeting as well as intracellular delivery. Numerous research groups are addressing these issues by advancing the development of nucleic acid medicines through nanotechnology. In countries other than Japan (including Europe and the USA), >40 nanotechnology-based nucleic acid medicines have been tested in clinical trials, and 15 clinical trials are ongoing. In Japan, three phase I trials are ongoing, and future results are awaited. The review summarizes the latest research in the nanotechnology of nucleic acid medicines and statuses of clinical trials in Japan, with expectations of further evolutions.

References

Wan Z, Gao X, Dong Y, Zhao Y, Chen X, Yang G . Exosome-mediated cell-cell communication in tumor progression. Am J Cancer Res. 2018; 8(9):1661-1673. PMC: 6176174. View

Maraganore J . Reflections on Alnylam. Nat Biotechnol. 2022; 40(5):641-650. DOI: 10.1038/s41587-022-01304-3. View

Roberts T, Langer R, Wood M . Advances in oligonucleotide drug delivery. Nat Rev Drug Discov. 2020; 19(10):673-694. PMC: 7419031. DOI: 10.1038/s41573-020-0075-7. View

Hoang Thi T, Suys E, Lee J, Nguyen D, Park K, Truong N . Lipid-Based Nanoparticles in the Clinic and Clinical Trials: From Cancer Nanomedicine to COVID-19 Vaccines. Vaccines (Basel). 2021; 9(4). PMC: 8069344. DOI: 10.3390/vaccines9040359. View

Li S, Hu Y, Li A, Lin J, Hsieh K, Schneiderman Z . Payload distribution and capacity of mRNA lipid nanoparticles. Nat Commun. 2022; 13(1):5561. PMC: 9508184. DOI: 10.1038/s41467-022-33157-4. View

Maeda H, Wu J, Sawa T, Matsumura Y, Hori K . Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J Control Release. 2000; 65(1-2):271-84. DOI: 10.1016/s0168-3659(99)00248-5. View

Crooke S, Vickers T, Liang X . Phosphorothioate modified oligonucleotide-protein interactions. Nucleic Acids Res. 2020; 48(10):5235-5253. PMC: 7261153. DOI: 10.1093/nar/gkaa299. View

Akinc A, Querbes W, De S, Qin J, Frank-Kamenetsky M, Narayanannair Jayaprakash K . Targeted delivery of RNAi therapeutics with endogenous and exogenous ligand-based mechanisms. Mol Ther. 2010; 18(7):1357-64. PMC: 2911264. DOI: 10.1038/mt.2010.85. View

Mendt M, Kamerkar S, Sugimoto H, McAndrews K, Wu C, Gagea M . Generation and testing of clinical-grade exosomes for pancreatic cancer. JCI Insight. 2018; 3(8). PMC: 5931131. DOI: 10.1172/jci.insight.99263. View

10.

Francia V, Schiffelers R, Cullis P, Witzigmann D . The Biomolecular Corona of Lipid Nanoparticles for Gene Therapy. Bioconjug Chem. 2020; 31(9):2046-2059. DOI: 10.1021/acs.bioconjchem.0c00366. View

11.

Nishimura T, Yamada A, Umezaki K, Sawada S, Mukai S, Sasaki Y . Self-Assembled Polypeptide Nanogels with Enzymatically Transformable Surface as a Small Interfering RNA Delivery Platform. Biomacromolecules. 2017; 18(12):3913-3923. DOI: 10.1021/acs.biomac.7b00937. View

12.

Du R, Cedrone E, Romanov A, Falkovich R, Dobrovolskaia M, Bathe M . Innate Immune Stimulation Using 3D Wireframe DNA Origami. ACS Nano. 2022; 16(12):20340-20352. PMC: 10144931. DOI: 10.1021/acsnano.2c06275. View

13.

Mu P, Nagahara S, Makita N, Tarumi Y, Kadomatsu K, Takei Y . Systemic delivery of siRNA specific to tumor mediated by atelocollagen: combined therapy using siRNA targeting Bcl-xL and cisplatin against prostate cancer. Int J Cancer. 2009; 125(12):2978-90. DOI: 10.1002/ijc.24382. View

14.

Kariko K, Muramatsu H, Welsh F, Ludwig J, Kato H, Akira S . Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability. Mol Ther. 2008; 16(11):1833-40. PMC: 2775451. DOI: 10.1038/mt.2008.200. View

15.

Perrault S, Shih W . Virus-inspired membrane encapsulation of DNA nanostructures to achieve in vivo stability. ACS Nano. 2014; 8(5):5132-40. PMC: 4046785. DOI: 10.1021/nn5011914. View

16.

Khvorova A, Watts J . The chemical evolution of oligonucleotide therapies of clinical utility. Nat Biotechnol. 2017; 35(3):238-248. PMC: 5517098. DOI: 10.1038/nbt.3765. View

17.

Liu K, Nilsson R, Lazaro-Ibanez E, Duan H, Miliotis T, Strimfors M . Multiomics analysis of naturally efficacious lipid nanoparticle coronas reveals high-density lipoprotein is necessary for their function. Nat Commun. 2023; 14(1):4007. PMC: 10325984. DOI: 10.1038/s41467-023-39768-9. View

18.

Jadhav V, Vaishnaw A, FitzGerald K, Maier M . RNA interference in the era of nucleic acid therapeutics. Nat Biotechnol. 2024; 42(3):394-405. DOI: 10.1038/s41587-023-02105-y. View

19.

Cheng M, Leung J, Zhang Y, Strong C, Basha G, Momeni A . Induction of Bleb Structures in Lipid Nanoparticle Formulations of mRNA Leads to Improved Transfection Potency. Adv Mater. 2023; 35(31):e2303370. DOI: 10.1002/adma.202303370. View

20.

Blanco E, Shen H, Ferrari M . Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nat Biotechnol. 2015; 33(9):941-51. PMC: 4978509. DOI: 10.1038/nbt.3330. View