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Review Article

RNA-based nanomedicines and their clinical applications

Lin-Jia Su1,§Zi-Han Ji1,2,§Mo-Xi Xu1,2,§Jia-Qing Zhu1,§Yi-Hai Chen1,3Jun-Fei Qiao1,4Yi Wang1,5( )Yao-Xin Lin1,2( )
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), Beijing 100190, China
University of Chinese Academy of Sciences (UCAS), Beijing 100149, China
Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin 150081, China
School of Chemical and Environmental Engineering, Wuhan Polytechnic University, Wuhan 430023, China
Institute of Bioengineering and Institute of Materials Science & Engineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, 1015, Switzerland

§ Lin-Jia Su, Zi-Han Ji, Mo-Xi Xu, and Jia-Qing Zhu contributed equally to this work.

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Graphical Abstract

With the quick developments of RNA-based technologies and delivery systems, these RNA-based nanomedicines have been widely developed and used in treatment of various diseases.

Abstract

RNA-based nanomedicines encompass a range of therapeutic approaches that utilize RNA molecules or molecules that target RNAs for the treatment or prevention of diseases. These include antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), endogenous microRNAs (miRNAs), messenger RNAs (mRNAs), clustered regularly interspersed short palindromic repeats-associated protein 9 (CRISPR/Cas9), single guide RNAs (sgRNAs), as well as RNA aptamers. These therapeutic agents exert their effects through various mechanisms such as gene inhibition, addition, replacement, and editing. The advancement of RNA biology and the field of RNA therapy has paved the way for the development and utilization of RNA-based nanomedicine in human healthcare. One remarkable example of RNA-based nanomedicine is the mRNA-based vaccines including mRNA-1273 (Moderna) and BNT162b2 (Pfizer/BioNTech) that have been successfully employed in response to the coronavirus disease 2019 (COVID-19) pandemic. This review aims to highlight the advantages of RNA-based nanomedicines, provides an overview of significant developments in delivery systems, elucidates the molecular mechanisms of action underlying RNA-based nanomedicines, and discusses their clinical applications. Additionally, the review will address the existing challenges and innovations in delivery platforms while exploring the future possibilities for these promising RNA-based nanomedicines.

References

[1]

Rich, A.; Davies, D. R. A new two stranded helical structure: Polyadenylic acid and polyuridylic acid. J. Am. Chem. Soc. 1956, 78, 3548–3549.

[2]

Lee, R. C.; Feinbaum, R. L.; Ambros, V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 1993, 75, 843–854.

[3]

Fire, A.; Xu, S. Q.; Montgomery, M. K.; Kostas, S. A.; Driver, S. E.; Mello, C. C. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 1998, 391, 806–811.

[4]

Crick, F. H. On protein synthesis. Symp. Soc. Exp. Biol. 1958, 12, 138–163.

[5]

Brenner, S.; Jacob, F.; Meselson, M. An unstable intermediate carrying information from genes to ribosomes for protein synthesis. Nature 1961, 190, 576–581.

[6]

Gros, F.; Hiatt, H.; Gilbert, W.; Kurland, C. G.; Risebrough, R. W.; Watson, J. D. Unstable ribonucleic acid revealed by pulse labelling of Escherichia coli. Nature 1961, 190, 581–585.

[7]

Berget, S. M.; Moore, C.; Sharp, P. A. Spliced segments at the 5’ terminus of adenovirus 2 late mRNA. Proc. Natl. Acad. Sci. USA 1977, 74, 3171–3175.

[8]

Chow, L. T.; Gelinas, R. E.; Broker, T. R.; Roberts, R. J. An amazing sequence arrangement at the 5’ ends of adenovirus 2 messenger RNA. Cell 1977, 12, 1–8.

[9]

Faustino, N. A.; Cooper, T. A. Pre-mRNA splicing and human disease. Genes Dev. 2003, 17, 419–437.

[10]

Scotti, M. M.; Swanson, M. S. RNA mis-splicing in disease. Nat. Rev. Genet. 2016, 17, 19–32.

[11]

Zamecnik, P. C.; Stephenson, M. L. Inhibition of Rous sarcoma virus replication and cell transformation by a specific oligodeoxynucleotide. Proc. Natl. Acad. Sci. USA 1978, 75, 280–284.

[12]

Dominski, Z.; Kole, R. Restoration of correct splicing in thalassemic pre-mRNA by antisense oligonucleotides. Proc. Natl. Acad. Sci. USA 1993, 90, 8673–8677.

[13]

Roehr, B. Fomivirsen approved for CMV retinitis. J. Int. Assoc. Physicians AIDS Care 1998, 4, 14–16.

[14]

Baltimore, D. Viral RNA-dependent DNA polymerase: RNA-dependent DNA polymerase in virions of RNA tumour viruses. Nature 1970, 226, 1209–1211.

[15]

Temin, H. M.; Mizutani, S. Viral RNA-dependent DNA polymerase: RNA-dependent DNA polymerase in virions of Rous sarcoma virus. Nature 1970, 226, 1211–1213.

[16]

Karikó, K.; Buckstein, M.; Ni, H. P.; Weissman, D. Suppression of RNA recognition by Toll-like receptors: The impact of nucleoside modification and the evolutionary origin of RNA. Immunity 2005, 23, 165–175.

[17]

Baden, L. R.; El Sahly, H. M.; Essink, B.; Kotloff, K.; Frey, S.; Novak, R.; Diemert, D.; Spector, S. A.; Rouphael, N.; Creech, C. B. et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N. Engl. J. Med. 2021, 384, 403–416.

[18]
Vogel, A. B.; Kanevsky, I.; Che, Y.; Swanson, K. A.; Muik, A.; Vormehr, M.; Kranz, L. M.; Walzer, K. C.; Hein, S.; Güler, A. et al. BNT162b vaccines protect rhesus macaques from SARS-CoV-2. Nature 2021 , 592, 283–289.
[19]

Jackson, L. A.; Anderson, E. J.; Rouphael, N. G.; Roberts, P. C.; Makhene, M.; Coler, R. N.; McCullough, M. P.; Chappell, J. D.; Denison, M. R.; Stevens, L. J. et al. An mRNA vaccine against SARS-CoV-2 - preliminary report. N. Engl. J. Med. 2020, 383, 1920–1931.

[20]

Mulligan, M. J.; Lyke, K. E.; Kitchin, N.; Absalon, J.; Gurtman, A.; Lockhart, S.; Neuzil, K.; Raabe, V.; Bailey, R.; Swanson, K. A. et al. Phase I/II study of COVID-19 RNA vaccine BNT162b1 in adults. Nature 2020, 586, 589–593.

[21]

Sahin, U.; Karikó, K.; Türeci, Ö. mRNA-based therapeutics-developing a new class of drugs. Nat. Rev. Drug Discov. 2014, 13, 759–780.

[22]

Ray, K. K.; Landmesser, U.; Leiter, L. A.; Kallend, D.; Dufour, R.; Karakas, M.; Hall, T.; Troquay, R. P. T.; Turner, T.; Visseren, F. L. J. et al. Inclisiran in patients at high cardiovascular risk with elevated LDL cholesterol. N. Engl. J. Med. 2017, 376, 1430–1440.

[23]

Esteller, M. Non-coding RNAs in human disease. Nat. Rev. Genet. 2011, 12, 861–874.

[24]

Song, J.; Kim, Y. K. Targeting non-coding RNAs for the treatment of retinal diseases. Mol. Ther. Nucl. Acids 2021, 24, 284–293.

[25]

Chen, B. B.; Altman, R. B. Opportunities for developing therapies for rare genetic diseases: Focus on gain-of-function and allostery. Orphanet J. Rare Dis. 2017, 12, 61.

[26]

Wang, F.; Zuroske, T.; Watts, J. K. RNA therapeutics on the rise. Nat. Rev. Drug Discov. 2020, 19, 441–442.

[27]

Houseley, J.; Tollervey, D. The many pathways of RNA degradation. Cell 2009, 136, 763–776.

[28]

Bryson, T. E.; Anglin, C. M.; Bridges, P. H.; Cottle, R. N. Nuclease-mediated gene therapies for inherited metabolic diseases of the liver. Yale J. Biol. Med. 2017, 90, 553–566.

[29]

Nguyen, G. N.; Everett, J. K.; Kafle, S.; Roche, A. M.; Raymond, H. E.; Leiby, J.; Wood, C.; Assenmacher, C. A.; Merricks, E. P.; Long, C. T. et al. A long-term study of AAV gene therapy in dogs with hemophilia a identifies clonal expansions of transduced liver cells. Nat. Biotechnol. 2021, 39, 47–55.

[30]

Wu, Z. J.; Yang, H. Y.; Colosi, P. Effect of genome size on AAV vector packaging. Mol. Ther. 2010, 18, 80–86.

[31]

Sugo, T.; Terada, M.; Oikawa, T.; Miyata, K.; Nishimura, S.; Kenjo, E.; Ogasawara-Shimizu, M.; Makita, Y.; Imaichi, S.; Murata, S. et al. Development of antibody-siRNA conjugate targeted to cardiac and skeletal muscles. J. Control. Release 2016, 237, 1–13.

[32]

Springer, A. D.; Dowdy, S. F. GalNAc-siRNA conjugates: Leading the way for delivery of RNAi therapeutics. Nucleic Acid Ther. 2018, 28, 109–118.

[33]

Schlegel, M. K.; Foster, D. J.; Kel'in, A. V.; Zlatev, I.; Bisbe, A.; Jayaraman, M.; Lackey, J. G.; Rajeev, K. G.; Charissé, K.; Harp, J. et al. Chirality dependent potency enhancement and structural impact of glycol nucleic acid modification on siRNA. J. Am. Chem. Soc. 2017, 139, 8537–8546.

[34]

Kumar, P.; Degaonkar, R.; Guenther, D. C.; Abramov, M.; Schepers, G.; Capobianco, M.; Jiang, Y. F.; Harp, J.; Kaittanis, C.; Janas, M. M. et al. Chimeric siRNAs with chemically modified pentofuranose and hexopyranose nucleotides: Altritol-nucleotide (ANA) containing GalNAc-siRNA conjugates: In vitro and in vivo RNAi activity and resistance to 5’-exonuclease. Nucleic Acids Res. 2020, 48, 4028–4040.

[35]

Balwani, M.; Sardh, E.; Ventura, P.; Peiró, P. A.; Rees, D. C.; Stölzel, U.; Bissell, D. M.; Bonkovsky, H. L.; Windyga, J.; Anderson, K. E. et al. Phase 3 trial of RNAi therapeutic givosiran for acute intermittent porphyria. N. Engl. J. Med. 2020, 382, 2289–2301.

[36]

Hom, C.; Lu, J.; Liong, M.; Luo, H. Z.; Li, Z. X.; Zink, J. I.; Tamanoi, F. Mesoporous silica nanoparticles facilitate delivery of siRNA to shutdown signaling pathways in mammalian cells. Small 2010, 6, 1185–1190.

[37]

Popat, A.; Hartono, S. B.; Stahr, F.; Liu, J.; Qiao, S. Z.; Lu, G. Q. Mesoporous silicananoparticles for bioadsorption, enzyme immobilisation, and delivery carriers. Nanoscale 2011, 3, 2801–2818.

[38]

Kim, J.; Eygeris, Y.; Gupta, M.; Sahay, G. Self-assembled mRNA vaccines. Adv. Drug Deliv. Rev. 2021, 170, 83–112.

[39]

Love, K. T.; Mahon, K. P.; Levins, C. G.; Whitehead, K. A.; Querbes, W.; Dorkin, J. R.; Qin, J.; Cantley, W.; Qin, L. L.; Racie, T. et al. Lipid-like materials for low-dose, in vivo gene silencing. Proc. Natl. Acad. Sci. USA 2010, 107, 1864–1869.

[40]

Dong, Y. Z.; Love, K. T.; Dorkin, J. R.; Sirirungruang, S.; Zhang, Y. L.; Chen, D. L.; Bogorad, R. L.; Yin, H.; Chen, Y.; Vegas, A. J. et al. Lipopeptide nanoparticles for potent and selective siRNA delivery in rodents and nonhuman primates. Proc. Natl. Acad. Sci. USA 2014, 111, 3955–3960.

[41]

Semple, S. C.; Akinc, A.; Chen, J. X.; Sandhu, A. P.; Mui, B. L.; Cho, C. K.; Sah, D. W. Y.; Stebbing, D.; Crosley, E. J.; Yaworski, E. et al. Rational design of cationic lipids for siRNA delivery. Nat. Biotechnol. 2010, 28, 172–176.

[42]

Jayaraman, M.; Ansell, S. M.; Mui, B. L.; Tam, Y. K.; Chen, J. X.; Du, X. Y.; Butler, D.; Eltepu, L.; Matsuda, S.; Narayanannair, J. K. et al. Maximizing the potency of siRNA lipid nanoparticles for hepatic gene silencing in vivo. Angew. Chem., Int. Ed. 2012, 51, 8529–8533.

[43]

Qiu, M.; Tang, Y.; Chen, J. J.; Muriph, R.; Ye, Z. F.; Huang, C. F.; Evans, J.; Henske, E. P.; Xu, Q. B. Lung-selective mRNA delivery of synthetic lipid nanoparticles for the treatment of pulmonary lymphangioleiomyomatosis. Proc. Natl. Acad. Sci. USA 2022, 119, e2116271119.

[44]

Cheng, Q.; Wei, T.; Farbiak, L.; Johnson, L. T.; Dilliard, S. A.; Siegwart, D. J. Selective organ targeting (SORT) nanoparticles for tissue-specific mRNA delivery and CRISPR-cas gene editing. Nat. Nanotechnol. 2020, 15, 313–320.

[45]

Kulkarni, J. A.; Cullis, P. R.; van der Meel, R. Lipid nanoparticles enabling gene therapies: From concepts to clinical utility. Nucleic Acid Ther. 2018, 28, 146–157.

[46]

Cheng, X. W.; Lee, R. J. The role of helper lipids in lipid nanoparticles (LNPs) designed for oligonucleotide delivery. Adv. Drug Deliv. Rev. 2016, 99, 129–137.

[47]

Dilliard, S. A.; Cheng, Q.; Siegwart, D. J. On the mechanism of tissue-specific mRNA delivery by selective organ targeting nanoparticles. Proc. Natl. Acad. Sci. USA 2021, 118, e2109256118.

[48]

Melamed, J. R.; Yerneni, S. S.; Arral, M. L.; LoPresti, S. T.; Chaudhary, N.; Sehrawat, A.; Muramatsu, H.; Alameh, M. G.; Pardi, N.; Weissman, D. et al. Ionizable lipid nanoparticles deliver mRNA to pancreatic β cells via macrophage-mediated gene transfer. Sci. Adv. 2023, 9, eade1444.

[49]
Li, B. W.; Manan, R. S.; Liang, S. Q.; Gordon, A.; Jiang, A.; Varley, A.; Gao, G. P.; Langer, R.; Xue, W.; Anderson, D. Combinatorial design of nanoparticles for pulmonary mRNA delivery and genome editing. Nat. Biotechnol., in press, DOI: 10.1038/s41587-023-01679-x.
[50]

Fornaguera, C.; Castells-Sala, C.; Lázaro, M. A.; Cascante, A.; Borrós, S. Development of an optimized freeze-drying protocol for OM-PBAE nucleic acid polyplexes. Int. J. Pharm. 2019, 569, 118612.

[51]

Boussif, O.; Lezoualc'h, F.; Zanta, M. A.; Mergny, M. D.; Scherman, D.; Demeneix, B.; Behr, J. P. A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: Polyethylenimine. Proc. Natl. Acad. Sci. USA 1995, 92, 7297–7301.

[52]

Ke, X. Y.; Shelton, L.; Hu, Y. Z.; Zhu, Y. N.; Chow, E.; Tang, H. Y.; Santos, J. L.; Mao, H. Q. Surface-functionalized PEGylated nanoparticles deliver messenger RNA to pulmonary immune cells. ACS Appl. Mater. Interfaces 2020, 12, 35835–35844.

[53]

Vaughan, H. J.; Zamboni, C. A. G.; Hassan, L. F.; Radant, N. P.; Jacob, D.; Mease, R. C.; Minn, I.; Tzeng, S. Y.; Gabrielson, K. L.; Bhardwaj, P. et al. Polymeric nanoparticles for dual-targeted theranostic gene delivery to hepatocellular carcinoma. Sci. Adv. 2022, 8, eabo6406.

[54]

Liu, S.; Wang, X.; Yu, X. L.; Cheng, Q.; Johnson, L. T.; Chatterjee, S.; Zhang, D.; Lee, S. M.; Sun, Y. H.; Lin, T. C. et al. Zwitterionic phospholipidation of cationic polymers facilitates systemic mRNA delivery to spleen and lymph nodes. J. Am. Chem. Soc. 2021, 143, 21321–21330.

[55]
Convertine, A. J.; Diab, C.; Prieve, M.; Paschal, A.; Hoffman, A. S.; Johnson, P. H.; Stayton, P. S. pH-responsive polymeric micelle carriers for siRNA drugs. Biomacromolecules 2010 , 11, 2904–2911.
[56]

Jacobson, M. E.; Wang-Bishop, L.; Becker, K. W.; Wilson, J. T. Delivery of 5’-triphosphate RNA with endosomolytic nanoparticles potently activates RIG-I to improve cancer immunotherapy. Biomater. Sci. 2019, 7, 547–559.

[57]

Kheraldine, H.; Rachid, O.; Habib, A. M.; Al Moustafa, A. E.; Benter, I. F.; Akhtar, S. Emerging innate biological properties of nano-drug delivery systems: A focus on PAMAM dendrimers and their clinical potential. Adv. Drug Deliv. Rev. 2021, 178, 113908.

[58]

Biswas, S.; Deshpande, P. P.; Navarro, G.; Dodwadkar, N. S.; Torchilin, V. P. Lipid modified triblock PAMAM-based nanocarriers for siRNA drug co-delivery. Biomaterials 2013, 34, 1289–1301.

[59]

Verminnen, K.; Beeckman, D. S. A.; Sanders, N. N.; De Smedt, S.; Vanrompay, D. C. G. Vaccination of turkeys against Chlamydophila psittaci through optimised DNA formulation and administration. Vaccine 2010, 28, 3095–3105.

[60]

Bøe, S. L.; Jørgensen, J. A. L.; Longva, A. S.; Lavelle, T.; Sæbøe-Larssen, S.; Hovig, E. Light-controlled modulation of gene expression using polyamidoamine formulations. Nucleic Acid Ther. 2013, 23, 160–165.

[61]

Deshayes, S.; Cabral, H.; Ishii, T.; Miura, Y.; Kobayashi, S.; Yamashita, T.; Matsumoto, A.; Miyahara, Y.; Nishiyama, N.; Kataoka, K. Phenylboronic acid-installed polymeric micelles for targeting sialylated epitopes in solid tumors. J. Am. Chem. Soc. 2013, 135, 15501–15507.

[62]

Oyewumi, M. O.; Yokel, R. A.; Jay, M.; Coakley, T.; Mumper, R. J. Comparison of cell uptake, biodistribution and tumor retention of folate-coated and PEG-coated gadolinium nanoparticles in tumor-bearing mice. J. Control. Release 2004, 95, 613–626.

[63]

Xiong, X. B.; Lavasanifar, A. Traceable multifunctional micellar nanocarriers for cancer-targeted co-delivery of MDR-1 siRNA and doxorubicin. ACS Nano 2011, 5, 5202–5213.

[64]

Xue, B.; Kozlovskaya, V.; Sherwani, M. A.; Ratnayaka, S.; Habib, S.; Anderson, T.; Manuvakhova, M.; Klampfer, L.; Yusuf, N.; Kharlampieva, E. Peptide-functionalized hydrogel cubes for active tumor cell targeting. Biomacromolecules 2018, 19, 4084–4097.

[65]

Mi, P.; Cabral, H.; Kataoka, K. Ligand-installed nanocarriers toward precision therapy. Adv. Mater. 2020, 32, 1902604.

[66]

Rotolo, L.; Vanover, D.; Bruno, N. C.; Peck, H. E.; Zurla, C.; Murray, J.; Noel, R. K.; O'Farrell, L.; Araínga, M.; Orr-Burks, N. et al. Species-agnostic polymeric formulations for inhalable messenger RNA delivery to the lung. Nat. Mater. 2023, 22, 369–379.

[67]

Go, Y. K.; Leal, C. Polymer-lipid hybrid materials. Chem. Rev. 2021, 121, 13996–14030.

[68]

Lin, Y. X.; Wang, Y.; Ding, J. X.; Jiang, A. P.; Wang, J.; Yu, M.; Blake, S.; Liu, S. S.; Bieberich, C. J.; Farokhzad, O. C. et al. Reactivation of the tumor suppressor PTEN by mRNA nanoparticles enhances antitumor immunity in preclinical models. Sci. Transl. Med. 2021, 13, eaba9772.

[69]

Li, Z. Y.; Zhang, X. Q.; Ho, W.; Bai, X.; Jaijyan, D. K.; Li, F. Q.; Kumar, R.; Kolloli, A.; Subbian, S.; Zhu, H. et al. Lipid-polymer hybrid “particle-in-particle” nanostructure gene delivery platform explored for lyophilizable DNA and mRNA COVID-19 vaccines. Adv. Funct. Mater. 2022, 32, 2204462.

[70]

Kowalski, P. S.; Rudra, A.; Miao, L.; Anderson, D. G. Delivering the messenger: Advances in technologies for therapeutic mRNA delivery. Mol. Ther. 2019, 27, 710–728.

[71]

Stephenson, M. L.; Zamecnik, P. C. Inhibition of Rous sarcoma viral RNA translation by a specific oligodeoxyribonucleotide. Proc. Natl. Acad. Sci. USA 1978, 75, 285–288.

[72]

Dhuri, K.; Bechtold, C.; Quijano, E.; Pham, H.; Gupta, A.; Vikram, A.; Bahal, R. Antisense oligonucleotides: An emerging area in drug discovery and development. J. Clin. Med. 2020, 9, 2004.

[73]

Quemener, A. M.; Bachelot, L.; Forestier, A.; Donnou-Fournet, E.; Gilot, D.; Galibert, M. D. The powerful world of antisense oligonucleotides: From bench to bedside. WIREs RNA 2020, 11, e1594.

[74]

Bennett, C. F. Therapeutic antisense oligonucleotides are coming of age. Annu. Rev. Med. 2019, 70, 307–321.

[75]

Li, Y. Q.; Chen, Y. T.; Li, J. J.; Zhang, Z. Q.; Huang, C. M.; Lian, G. D.; Yang, K. G.; Chen, S. J.; Lin, Y.; Wang, L. Y. et al. Co-delivery of microRNA-21 antisense oligonucleotides and gemcitabine using nanomedicine for pancreatic cancer therapy. Cancer Sci. 2017, 108, 1493–1503.

[76]

Sun, Y.; Cai, M. X.; Zhong, J. Y.; Yang, L.; Xiao, J.; Jin, F. J.; Xue, H.; Liu, X. N.; Liu, H. S.; Zhang, Y. B. et al. The long noncoding RNA lnc-ob1 facilitates bone formation by upregulating Osterix in osteoblasts. Nat. Metab. 2019, 1, 485–496.

[77]

Migliorati, J. M.; Liu, S. N.; Liu, A. N.; Gogate, A.; Nair, S.; Bahal, R.; Rasmussen, T. P.; Manautou, J. E.; Zhong, X. B. Absorption, distribution, metabolism, and excretion of US food and drug administration-approved antisense oligonucleotide drugs. Drug Metab. Dispos. 2022, 50, 888–897.

[78]

Crooke, S. T.; Liang, X. H.; Crooke, R. M.; Baker, B. F.; Geary, R. S. Antisense drug discovery and development technology considered in a pharmacological context. Biochem. Pharmacol. 2021, 189, 114196.

[79]

Reilley, M. J.; McCoon, P.; Cook, C.; Lyne, P.; Kurzrock, R.; Kim, Y.; Woessner, R.; Younes, A.; Nemunaitis, J.; Fowler, N. et al. STAT3 antisense oligonucleotide AZD9150 in a subset of patients with heavily pretreated lymphoma: Results of a phase 1b trial. J. Immunother. Cancer 2018, 6, 119.

[80]

Odate, S.; Veschi, V.; Yan, S.; Lam, N.; Woessner, R.; Thiele, C. J. Inhibition of STAT3 with the generation 2.5 antisense oligonucleotide, AZD9150, decreases neuroblastoma tumorigenicity and increases chemosensitivity. Clin. Cancer Res. 2017, 23, 1771–1784.

[81]

Jaschinski, F.; Rothhammer, T.; Jachimczak, P.; Seitz, C.; Schneider, A.; Schlingensiepen, K. H. The antisense oligonucleotide trabedersen (AP 12009) for the targeted inhibition of TGF-β2. Curr. Pharm. Biotechnol. 2011, 12, 2203–2013.

[82]

Chi, K. N.; Higano, C. S.; Blumenstein, B.; Ferrero, J. M.; Reeves, J.; Feyerabend, S.; Gravis, G.; Merseburger, A. S.; Stenzl, A.; Bergman, A. M. et al. Custirsen in combination with docetaxel and prednisone for patients with metastatic castration-resistant prostate cancer (SYNERGY trial): A phase 3, multicentre, open-label, randomised trial. Lancet Oncol. 2017, 18, 473–485.

[83]

Rosenberg, J. E.; Hahn, N. M.; Regan, M. M.; Werner, L.; Alva, A.; George, S.; Picus, J.; Alter, R.; Balar, A.; Hoffman-Censits, J. et al. Apatorsen plus docetaxel versus docetaxel alone in platinum-resistant metastatic urothelial carcinoma (Borealis-2). Br. J. Cancer 2018, 118, 1434–1441.

[84]

Harada, T.; Matsumoto, S.; Hirota, S.; Kimura, H.; Fujii, S.; Kasahara, Y.; Gon, H.; Yoshida, T.; Itoh, T.; Haraguchi, N. et al. Chemically modified antisense oligonucleotide against ARL4C inhibits primary and metastatic liver tumor growth. Mol. Cancer Ther. 2019, 18, 602–612.

[85]

Jiang, M. C.; Ni, J. J.; Cui, W. Y.; Wang, B. Y.; Zhuo, W. Emerging roles of lncRNA in cancer and therapeutic opportunities. Am. J. Cancer Res. 2019, 9, 1354–1366.

[86]

Huarte, M. The emerging role of lncRNAs in cancer. Nat. Med. 2015, 21, 1253–1261.

[87]

Kara, G.; Calin, G. A.; Ozpolat, B. RNAi-based therapeutics and tumor targeted delivery in cancer. Adv. Drug Deliv. Rev. 2022, 182, 114113.

[88]

Hu, B.; Zhong, L. P.; Weng, Y. H.; Peng, L.; Huang, Y. Y.; Zhao, Y. X.; Liang, X. J. Therapeutic siRNA: State of the art. Signal Transduct. Target. Ther. 2020, 5, 101.

[89]

Subhan, M. A.; Attia, S. A.; Torchilin, V. P. Advances in siRNA delivery strategies for the treatment of MDR cancer. Life Sci. 2021, 274, 119337.

[90]

Bai, X.; Zhao, G. L.; Chen, Q. J.; Li, Z. Y.; Gao, M. Z.; Ho, W.; Xu, X. Y.; Zhang, X. Q. Inhaled siRNA nanoparticles targeting IL11 inhibit lung fibrosis and improve pulmonary function post-bleomycin challenge. Sci. Adv. 2022, 8, eabn7162.

[91]

Zhou, Y. Y.; Zhu, F. Y.; Liu, Y.; Zheng, M.; Wang, Y. B.; Zhang, D. Y.; Anraku, Y.; Zou, Y.; Li, J.; Wu, H. G. et al. Blood-brain barrier-penetrating siRNA nanomedicine for Alzheimer's disease therapy. Sci. Adv. 2020, 6, eabc7031.

[92]

Lekka, E.; Hall, J. Noncoding RNAs in disease. FEBS Lett. 2018, 592, 2884–2900.

[93]

Hong, D. S.; Kang, Y. K.; Borad, M.; Sachdev, J.; Ejadi, S.; Lim, H. Y.; Brenner, A. J.; Park, K.; Lee, J. L.; Kim, T. Y. et al. Phase 1 study of MRX34, a liposomal miR-34a mimic, in patients with advanced solid tumours. Br. J. Cancer 2020, 122, 1630–1637.

[94]

Panigrahi, M.; Palmer, M. A.; Wilson, J. A. MicroRNA-122 regulation of HCV infections: Insights from studies of miR-122-independent replication. Pathogens 2022, 11, 1005.

[95]

Hinkel, R.; Penzkofer, D.; Zühlke, S.; Fischer, A.; Husada, W.; Xu, Q. F.; Baloch, E.; van Rooij, E.; Zeiher, A. M.; Kupatt, C. et al. Inhibition of microRNA-92a protects against ischemia/reperfusion injury in a large-animal model. Circulation 2013, 128, 1066–1075.

[96]
Tang, J. M.; Li, X.; Cheng, T. L.; Wu, J. miR-21-5p/SMAD7 axis promotes the progress of lung cancer. Thorac Cancer 2021 , 12, 2307–2313.
[97]
Zhen, C. L.; Wu, X. X.; Zhang, J.; Liu, D.; Li, G. L.; Yan, Y. B.; He, X. Z.; Miao, J. W.; Song, H. X.; Yan, Y. F. et al. Ganoderma lucidum polysaccharides attenuates pressure-overload-induced pathological cardiac hypertrophy. Front. Pharmacol. 2023 , 14, 1127123.
[98]

Jiang, F. G.; Doudna, J. A. CRISPR-Cas9 structures and mechanisms. Annu. Rev. Biophys. 2017, 46, 505–529.

[99]

Zhang, H. M.; Qin, C. H.; An, C. M.; Zheng, X. W.; Wen, S. X.; Chen, W. J.; Liu, X. F.; Lv, Z. H.; Yang, P. C.; Xu, W. et al. Application of the CRISPR/Cas9-based gene editing technique in basic research, diagnosis, and therapy of cancer. Mol. Cancer 2021, 20, 126.

[100]

Jinek, M.; Chylinski, K.; Fonfara, I.; Hauer, M.; Doudna, J. A.; Charpentier, E. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 2012, 337, 816–821.

[101]

Westermann, L.; Neubauer, B.; Köttgen, M. Nobel Prize 2020 in Chemistry honors CRISPR: A tool for rewriting the code of life. Pflugers Arch. 2021, 473, 1–2.

[102]

Sharma, G.; Sharma, A. R.; Bhattacharya, M.; Lee, S. S.; Chakraborty, C. CRISPR-Cas9: A preclinical and clinical perspective for the treatment of human diseases. Mol. Ther. 2021, 29, 571–586.

[103]

Anzalone, A. V.; Randolph, P. B.; Davis, J. R.; Sousa, A. A.; Koblan, L. W.; Levy, J. M.; Chen, P. J.; Wilson, C.; Newby, G. A.; Raguram, A. et al. Search-and-replace genome editing without double-strand breaks or donor DNA. Nature 2019, 576, 149–157.

[104]

Chen, B. H.; Gilbert, L. A.; Cimini, B. A.; Schnitzbauer, J.; Zhang, W.; Li, G. W.; Park, J.; Blackburn, E. H.; Weissman, J. S.; Qi, L. S. et al. Dynamic imaging of genomic loci in living human cells by an optimized CRISPR/Cas system. Cell 2013, 155, 1479–1491.

[105]

Frangoul, H.; Altshuler, D.; Cappellini, M. D.; Chen, Y. S.; Domm, J.; Eustace, B. K.; Foell, J.; de la Fuente, J.; Grupp, S.; Handgretinger, R. et al. CRISPR-Cas9 gene editing for sickle cell disease and β-thalassemia. N. Engl. J. Med. 2021, 384, 252–260.

[106]

Qin, R. Y.; Li, J.; Liu, X. S.; Xu, R. F.; Yang, J. B.; Wei, P. C. SpCas9-NG self-targets the sgRNA sequence in plant genome editing. Nat. Plants 2020, 6, 197–201.

[107]
Li, C.; Zong, Y.; Jin, S.; Zhu, H. C.; Lin, D. X.; Li, S. N.; Qiu, J. L.; Wang, Y. P.; Gao, C. X. SWISS: Multiplexed orthogonal genome editing in plants with a Cas9 nickase and engineered CRISPR RNA scaffolds. Genome Biol. 2020 , 21, 141.
[108]

Liu, L.; Li, W. B.; Li, J.; Zhao, D. D.; Li, S. W.; Jiang, G.; Wang, J.; Chen, X. X.; Bi, C. H.; Zhang, X. L. Circular guide RNA for improved stability and CRISPR-Cas9 editing efficiency in vitro and in bacteria. ACS Synth. Biol. 2023, 12, 350–359.

[109]

Locatelli, F.; Lang, P.; Li, A.; Corbacioglu, S.; de la Fuente, J.; Wall, D. A.; Liem, R.; Meisel, R.; Mapara, M. Y.; Shah, A. J. et al. Efficacy and safety of a single dose of exagamglogene autotemcel for transfusion-dependent β-thalassemia. Blood 2022, 140, 4899–4901.

[110]

Abraham, A. A.; Tisdale, J. F. Gene therapy for sickle cell disease: Moving from the bench to the bedside. Blood 2021, 138, 932–941.

[111]

Ren, J. T.; Liu, X. J.; Fang, C. Y.; Jiang, S. G.; June, C. H.; Zhao, Y. B. Multiplex genome editing to generate universal CAR T Cells resistant to PD1 inhibition. Clin. Cancer Res. 2017, 23, 2255–2266.

[112]

Mascola, J. R.; Fauci, A. S. Novel vaccine technologies for the 21st century. Nat. Rev. Immunol. 2020, 20, 87–88.

[113]

Wolff, J. A.; Malone, R. W.; Williams, P.; Chong, W.; Acsadi, G.; Jani, A.; Felgner, P. L. Direct gene transfer into mouse muscle in vivo. Science 1990, 247, 1465–1468.

[114]

Lorentzen, C. L.; Haanen, J. B.; Met, Ö.; Svane, I. M. Clinical advances and ongoing trials of mRNA vaccines for cancer treatment. Lancet Oncol. 2022, 23, e450–e458.

[115]

Pardi, N.; Hogan, M. J.; Porter, F. W.; Weissman, D. mRNA vaccines - a new era in vaccinology. Nat. Rev. Drug Discov. 2018, 17, 261–279.

[116]

Luo, M.; Wang, H.; Wang, Z. H.; Cai, H. C.; Lu, Z. G.; Li, Y.; Du, M. J.; Huang, G.; Wang, C. S.; Chen, X. et al. A STING-activating nanovaccine for cancer immunotherapy. Nat. Nanotechnol. 2017, 12, 648–654.

[117]

Li, S. X.; Luo, M.; Wang, Z. H.; Feng, Q.; Wilhelm, J.; Wang, X.; Li, W.; Wang, J.; Cholka, A.; Fu, Y. X. et al. Prolonged activation of innate immune pathways by a polyvalent STING agonist. Nat. Biomed. Eng. 2021, 5, 455–466.

[118]

Zhou, K. J.; Nguyen, L. H.; Miller, J. B.; Yan, Y. F.; Kos, P.; Xiong, H.; Li, L.; Hao, J.; Minnig, J. T.; Zhu, H. et al. Modular degradable dendrimers enable small RNAs to extend survival in an aggressive liver cancer model. Proc. Natl. Acad. Sci. USA 2016, 113, 520–525.

[119]

Cheng, Q.; Wei, T.; Jia, Y. M.; Farbiak, L.; Zhou, K. J.; Zhang, S. Y.; Wei, Y. L.; Zhu, H.; Siegwart, D. J. Dendrimer-based lipid nanoparticles deliver therapeutic FAH mRNA to normalize liver function and extend survival in a mouse model of hepatorenal tyrosinemia type I. Adv. Mater. 2018, 30, 1805308.

[120]

Rurik, J. G.; Tombácz, I.; Yadegari, A.; Fernández, P. O. M.; Shewale, S. V.; Li, L.; Kimura, T.; Soliman, O. Y.; Papp, T. E.; Tam, Y. K. et al. CAR T cells produced in vivo to treat cardiac injury. Science 2022, 375, 91–96.

[121]

Segel, M.; Lash, B.; Song, J. W.; Ladha, A.; Liu, C. C.; Jin, X.; Mekhedov, S. L.; Macrae, R. K.; Koonin, E. V.; Zhang, F. Mammalian retrovirus-like protein PEG10 packages its own mRNA and can be pseudotyped for mRNA delivery. Science 2021, 373, 882–889.

[122]

Kutzler, M. A.; Weiner, D. B. DNA vaccines: Ready for prime time. Nat. Rev. Genet. 2008, 9, 776–788.

[123]

Huang, X. G.; Kong, N.; Zhang, X. C.; Cao, Y. H.; Langer, R.; Tao, W. The landscape of mRNA nanomedicine. Nat. Med. 2022, 28, 2273–2287.

[124]

Andries, O.; Mc Cafferty, S.; De Smedt, S. C.; Weiss, R.; Sanders, N. N.; Kitada, T. N1-methylpseudouridine-incorporated mRNA outperforms pseudouridine-incorporated mRNA by providing enhanced protein expression and reduced immunogenicity in mammalian cell lines and mice. J. Control. Release 2015, 217, 337–344.

[125]

Barbier, A. J.; Jiang, A. Y.; Zhang, P.; Wooster, R.; Anderson, D. G. The clinical progress of mRNA vaccines and immunotherapies. Nat. Biotechnol. 2022, 40, 840–854.

[126]

Chaudhary, N.; Weissman, D.; Whitehead, K. A. mRNA vaccines for infectious diseases: Principles, delivery and clinical translation. Nat. Rev. Drug Discov. 2021, 20, 817–838.

[127]

Yu, M. Z.; Wang, N. N.; Zhu, J. Q.; Lin, Y. X. The clinical progress and challenges of mRNA vaccines. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 2023, 15, e1894.

[128]

Zhang, H. X.; Zhang, Y.; Yin, H. Genome editing with mRNA encoding ZFN, TALEN, and Cas9. Mol. Ther. 2019, 27, 735–746.

[129]
Kim, M. Y.; Jeong, S. In vitro selection of RNA aptamer and specific targeting of ErbB2 in breast cancer cells. Nucleic Acid Ther. 2011 , 21, 173–178.
[130]

Tan, W. H.; Wang, H.; Chen, Y.; Zhang, X. B.; Zhu, H. Z.; Yang, C. Y.; Yang, R. H.; Liu, C. Molecular aptamers for drug delivery. Trends Biotechnol. 2011, 29, 634–640.

[131]

Camorani, S.; d’Argenio, A.; Agnello, L.; Nilo, R.; Zannetti, A.; Ibarra, L. E.; Fedele, M.; Cerchia, L. Optimization of short RNA aptamers for TNBC cell targeting. Int. J. Mol. Sci. 2022, 23, 3511.

[132]

Guo, P. X.; Coban, O.; Snead, N. M.; Trebley, J.; Hoeprich, S.; Guo, S. C.; Shu, Y. Engineering RNA for targeted siRNA delivery and medical application. Adv. Drug Deliv. Rev. 2010, 62, 650–666.

[133]

Zhu, Y.; Hart, G. W. Dual-specificity RNA aptamers enable manipulation of target-specific O-GlcNAcylation and unveil functions of O-GlcNAc on β-catenin. Cell 2023, 186, 428–445.e27.

[134]

Kim, J.; Piao, Y. Z.; Hyeon, T. Multifunctional nanostructured materials for multimodal imaging, and simultaneous imaging and therapy. Chem. Soc. Rev. 2009, 38, 372–390.

[135]

Röthlisberger, P.; Gasse, C.; Hollenstein, M. Nucleic acid aptamers: Emerging applications in medical imaging, nanotechnology, neurosciences, and drug delivery. Int. J. Mol. Sci. 2017, 18, 2430.

[136]

Willner, I.; Willner, B. Biomolecule-based nanomaterials and nanostructures. Nano Lett. 2010, 10, 3805–3815.

[137]

Jones, C. H.; Chen, C. K.; Ravikrishnan, A.; Rane, S.; Pfeifer, B. A. Overcoming nonviral gene delivery barriers: Perspective and future. Mol. Pharmaceutics 2013, 10, 4082–4098.

[138]
Popa, S. J.; Stewart, S. E. Socially distanced intercellular communication: Mechanisms for extracellular vesicle cargo delivery. In New Frontiers: Extracellular Vesicles. Mathivanan, S.; Fonseka, P.; Nedeva, C.; Atukorala, I., Eds.; Springer: Cham, 2021; pp 179–209.
[139]

Nimjee, S. M.; White, R. R.; Becker, R. C.; Sullenger, B. A. Aptamers as therapeutics. Annu. Rev. Pharmacol. Toxicol. 2017, 57, 61–79.

[140]

Zhou, C.; He, X.; Tong, C.; Li, H. H.; Xie, C. F.; Wu, Y. D.; Wang, L. L.; Yan, X. H.; Luo, D. Y.; Tang, Y. P. et al. Cancer-associated adipocytes promote the invasion and metastasis in breast cancer through LIF/CXCLs positive feedback loop. Int. J. Biol. Sci. 2022, 18, 1363–1380.

[141]

Steurer, M.; Montillo, M.; Scarfò, L.; Mauro, F. R.; Andel, J.; Wildner, S.; Trentin, L.; Janssens, A.; Burgstaller, S.; Frömming, A. et al. Olaptesed pegol (NOX-A12) with bendamustine and rituximab: A phase IIa study in patients with relapsed/refractory chronic lymphocytic leukemia. Haematologica 2019, 104, 2053–2060.

[142]

Marasca, R.; Maffei, R. NOX-A12: Mobilizing CLL away from home. Blood 2014, 123, 952–953.

[143]

Bie, L. H.; Wang, Y.; Jiang, F. Z.; Xiao, Z.; Zhang, L. J.; Wang, J. Insights into the binding mode of AS1411 aptamer to nucleolin. Front. Mol. Biosci. 2022, 9, 1025313.

[144]
Rosenberg, J. E.; Bambury, R. M.; van Allen, E. M.; Drabkin, H. A.; Lara, P. N. Jr.; Harzstark, A. L.; Wagle, N.; Figlin, R. A.; Smith, G. W.; Garraway, L. A. et al. A phase II trial of AS1411 (a novel nucleolin-targeted DNA aptamer) in metastatic renal cell carcinoma. Invest. New Drugs 2014 , 32, 178–187.
[145]

Taneja, V.; Goel, M.; Shankar, U.; Kumar, A.; Khilnani, G. C.; Prasad, H. K.; Prasad, G. B. K. S.; Gupta, U. D.; Sharma, T. K. An aptamer linked immobilized sorbent assay (ALISA) to detect circulatory IFN-α, an inflammatory protein among tuberculosis patients. ACS Comb. Sci. 2020, 22, 656–666.

[146]

Gruenke, P. R.; Aneja, R.; Welbourn, S.; Ukah, O. B.; Sarafianos, S. G.; Burke, D. H.; Lange, M. J. Selection and identification of an RNA aptamer that specifically binds the HIV-1 capsid lattice and inhibits viral replication. Nucleic Acids Res. 2022, 50, 1701–1717.

[147]

Garred, P.; Tenner, A. J.; Mollnes, T. E. Therapeutic targeting of the complement system: From rare diseases to pandemics. Pharmacol. Rev. 2021, 73, 792–827.

[148]

Diaz, J. A.; Wrobleski, S. K.; Alvarado, C. M.; Hawley, A. E.; Doornbos, N. K.; Lester, P. A.; Lowe, S. E.; Gabriel, J. E.; Roelofs, K. J.; Henke, P. K. et al. P-selectin inhibition therapeutically promotes thrombus resolution and prevents vein wall fibrosis better than enoxaparin and an inhibitor to von Willebrand factor. Arterioscler. Thromb. Vasc. Biol. 2015, 35, 829–837.

Nano Research
Pages 13182-13204
Cite this article:
Su L-J, Ji Z-H, Xu M-X, et al. RNA-based nanomedicines and their clinical applications. Nano Research, 2023, 16(12): 13182-13204. https://doi.org/10.1007/s12274-023-6238-5
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RNA
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Received: 26 June 2023
Revised: 26 September 2023
Accepted: 30 September 2023
Published: 01 December 2023
© Tsinghua University Press 2023
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