Exploration of Targeted Anti-tumor Therapy

Table 4. Food and Drug Administration (FDA) and/or European Medicines Agency (EMA) approved RNA drugs are currently in clinical use.

RNA type	Drug	Brand name	FDA approval	Company	Indication	Delivery system	Target gene
ASO	Fomivirsen	Vitravene	1998 (Withdrawn)	Ionis/Novartis	CMV retinitis	Naked	IE2
	Mipomersen	Kynamro	2013 (Withdrawn)	Kastle/Ionis	HoFH	Naked	APOB-100
	Nusinersen	Spinraza	2016	Ionis/Biogen	SMA	Naked	SMN2
	Eteplirsen	Exondys	2016	Sarepta	DMD	Naked	DMD
	Inotersen	Tegsedi	2018	Ionis	hATTR-PN	Naked	TTR
	Volanesorsen	Waylivra	2019	Ionis	FCS	Naked	APOC3
	Golodirsen	Vyondys 53	2019	Sarepta	DMD	Naked	DMD
	Viltolarsen	Viltepso	2020	Nippon Shinyaku	DMD	Naked	DMD
	Casimersen	Amondys 45	2021	Sarepta	DMD	Naked	DMD
	Tofersen	Qalsody	2023	Ionis/Biogen	SOD1-ALS	Naked	SOD1
	Eplontersen	Wainua	2023	AstraZeneca/Ionis	hATTR-PN	GalNAc	TTR
	Imetelstat	Rytelo	2024	Geron Corporation	MDS	Naked	hTERT
	Olezarsen	Tryngolza	2024	Ionis	FCS	GalNAc	APOC3
siRNA	Patisiran	Onpattro	2018	Alnylam	hATTR-PN	LNP	TTR
	Givosiran	Givlaari	2019	Alnylam	AHP	GalNAc	ALAS1
	Lumasiran	Oxlumo	2020	Alnylam	PH1	GalNAc	HAO1
	Inclisiran	Leqvio	2021	Novartis	HoFH	GalNAc	PCSK9
	Vutrisiran	Amvuttra	2022	Alnylam	hATTR-PN	GalNAc	TTR
	Nedosiran	Rivfloza	2023	Novo Nordisk	PH1	GalNAc	LDHA
Aptamer	Pegaptanib	Macugen	2004 (Withdrawn)	Pfizer/Eyetech	wAMD	PEG	VEGF
	Avacincaptad pegol	IZERVAY	2023	Archemix/Iveric Bio	GA	PEG	C5 protein

Return to article view

AHP: acute hepatic porphyria; ALAS1: aminolevulinic acid synthase 1; ASO: anti-sense oligo; CMV: cytomegalovirus; DMD: Duchenne muscular dystrophy; FCS: familial chylomicronemia syndrome; GA: geographic atrophy; GalNAc: N-acetylgalactosamine; HAO1: hydroxyacid oxidase 1; hATTR-PN: hereditary transthyretin-mediated amyloidosis with polyneuropathy; HoFH: homozygous familial hypercholesterolemia; LDHA: lactate dehydrogenase A; MDS: myelodysplastic syndromes; PH1: primary hyperoxaluria type 1; siRNA: short-interference RNA; SMA: spinal muscular atrophy; SOD1-ALS: amyotrophic lateral sclerosis caused by superoxide dismutase 1 mutation; VEGF: vascular endothelial growth factor; wAMD: wet age-related macular degeneration. Adapted with permission from Biopharma PEG: https://www.biochempeg.com/article/410.html#:~:text=Nucleic%20acid%20drugs%2C%20also%20known,are%20siRNA%20and%20ASO%20therapies. Accessed November 8, 2025. © Biopharma PEG Scientific Inc.

Declarations

Acknowledgments

During the preparation of this work, the author(s) used OpenAI (ChatGPT) for Figure 3 generation after feeding the AI with the authors’ idea. After using the tool, author(s) reviewed and edited the content as needed and take(s) full responsibility for the content of the publication.

Author contributions

AAI: Conceptualization, Writing—original draft, Resources, Writing—review & editing, Supervision, Project administration. NDV: Resources, Writing—original draft, Writing—review & editing. BL: Conceptualization, Resources, Writing—original draft, Writing—review & editing. All authors read and approved the submitted version.

Conflicts of interest

The authors declare that there are no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

Not applicable.

Copyright

Publisher’s note

Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.

References

Teicher BA. Perspective: Opportunities in recalcitrant, rare and neglected tumors. Oncol Rep. 2013;30:1030–4. [DOI] [PubMed] [PMC]

Gazdar AF, Minna JD. Developing New, Rational Therapies for Recalcitrant Small Cell Lung Cancer. J Natl Cancer Inst. 2016;108:djw119. [DOI] [PubMed]

Pillai RK, Jayasree K. Rare cancers: Challenges & issues. Indian J Med Res. 2017;145:17–27. [DOI] [PubMed] [PMC]

Cancer Facts & Figures 2025 [Internet]. American Cancer Society; c2025 [cited 2026 Jan 4, 2026]. Available from: https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/2025-cancer-facts-figures.html

Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024;74:12–49. [DOI] [PubMed]

Polley E, Kunkel M, Evans D, Silvers T, Delosh R, Laudeman J, et al. Small Cell Lung Cancer Screen of Oncology Drugs, Investigational Agents, and Gene and microRNA Expression. J Natl Cancer Inst. 2016;108:djw122. [DOI] [PubMed] [PMC]

Dómine M, Moran T, Isla D, Martí JL, Sullivan I, Provencio M, et al. SEOM clinical guidelines for the treatment of small-cell lung cancer (SCLC) (2019). Clin Transl Oncol. 2020;22:245–55. [DOI] [PubMed]

Sen T. Identifying and targeting the Achilles heel of a recalcitrant cancer. Sci Transl Med. 2021;13:eabj6946. [DOI] [PubMed]

Progress in Small Cell Lung Cancer (SCLC) Research Working Group 2019 [Internet]. National Cancer Institute Clinical Trials and Translational Research Advisory Committee (CTAC); c2019 [cited 2025 Oct 19]. Available from: https://web.archive.org/web/20250205044900/https:/deainfo.nci.nih.gov/advisory/ctac/0719/Att%2013_SCLC%20PWG%20Final%20Report_CTAC%20071719_v2.pdf

10.

Progress in Pancreatic Ductal Adenocarcinoma (PDAC) Research Working Group [Internet]. National Cancer Institute Clinical Trials and Translational Research Advisory Committee (CTAC); c2019 [cited 2025 Oct 19]. Available from: https://web.archive.org/web/20250202062603/https:/deainfo.nci.nih.gov/advisory/ctac/workgroup/PDAC/WGreport2019.pdf

11.

Zhu Y, Zhu L, Wang X, Jin H. RNA-based therapeutics: an overview and prospectus. Cell Death Dis. 2022;13:644. [DOI] [PubMed] [PMC]

12.

Yarmishyn AA, Ishola AA, Chen CY, Verusingam ND, Rengganaten V, Mustapha HA, et al. Circular RNAs Modulate Cancer Hallmark and Molecular Pathways to Support Cancer Progression and Metastasis. Cancers (Basel). 2022;14:862. [DOI] [PubMed] [PMC]

13.

Guan L, Hao Q, Shi F, Gao B, Wang M, Zhou X, et al. Regulation of the tumor immune microenvironment by cancer-derived circular RNAs. Cell Death Dis. 2023;14:132. [DOI] [PubMed] [PMC]

14.

Liu T, Long K, Zhu Z, Song Y, Chen C, Xu G, et al. Roles of circRNAs in regulating the tumor microenvironment. Med Oncol. 2023;40:329. [DOI] [PubMed] [PMC]

15.

Wang YS, Kumari M, Chen GH, Hong MH, Yuan JP, Tsai JL, et al. mRNA-based vaccines and therapeutics: an in-depth survey of current and upcoming clinical applications. J Biomed Sci. 2023;30:84. [DOI] [PubMed] [PMC]

16.

Gazdar AF, Bunn PA, Minna JD. Small-cell lung cancer: what we know, what we need to know and the path forward. Nat Rev Cancer. 2017;17:725–37. [DOI] [PubMed]

17.

Sabari JK, Lok BH, Laird JH, Poirier JT, Rudin CM. Unravelling the biology of SCLC: implications for therapy. Nat Rev Clin Oncol. 2017;14:549–61. [DOI] [PubMed] [PMC]

18.

Tariq S, Kim SY, Monteiro de Oliveira Novaes J, Cheng H. Update 2021: Management of Small Cell Lung Cancer. Lung. 2021;199:579–87. [DOI] [PubMed]

19.

Wang S, Tang J, Sun T, Zheng X, Li J, Sun H, et al. Survival changes in patients with small cell lung cancer and disparities between different sexes, socioeconomic statuses and ages. Sci Rep. 2017;7:1339. [DOI] [PubMed] [PMC]

20.

Lewis DR, Check DP, Caporaso NE, Travis WD, Devesa SS. US lung cancer trends by histologic type. Cancer. 2014;120:2883–92. [DOI] [PubMed] [PMC]

21.

Pavlidis ET, Galanis IN, Pavlidis TE. Updates in the diagnosis and management of ductal adenocarcinoma of the pancreas. World J Clin Oncol. 2025;16:105601. [DOI] [PubMed] [PMC]

22.

Halbrook CJ, Lyssiotis CA, Pasca di Magliano M, Maitra A. Pancreatic cancer: Advances and challenges. Cell. 2023;186:1729–54. [DOI] [PubMed] [PMC]

23.

Stoop TF, Javed AA, Oba A, Koerkamp BG, Seufferlein T, Wilmink JW, et al. Pancreatic cancer. Lancet. 2025;405:1182–202. [DOI] [PubMed]

24.

Principe DR, Underwood PW, Korc M, Trevino JG, Munshi HG, Rana A. The Current Treatment Paradigm for Pancreatic Ductal Adenocarcinoma and Barriers to Therapeutic Efficacy. Front Oncol. 2021;11:688377. [DOI] [PubMed] [PMC]

25.

Blackford AL, Canto MI, Klein AP, Hruban RH, Goggins M. Recent Trends in the Incidence and Survival of Stage 1A Pancreatic Cancer: A Surveillance, Epidemiology, and End Results Analysis. J Natl Cancer Inst. 2020;112:1162–69. [DOI] [PubMed] [PMC]

26.

Cancer Facts & Figures 2010 [Internet]. American Cancer Society; c2010 [cited 2025 Oct 19]. Available from: https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2010.html

27.

Kleeff J, Michalski C, Friess H, Büchler MW. Pancreatic cancer: from bench to 5-year survival. Pancreas. 2006;33:111–8. [DOI] [PubMed]

28.

Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60:277–300. [DOI] [PubMed]

29.

Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64:9–29. [DOI] [PubMed]

30.

Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63:11–30. [DOI] [PubMed]

31.

Siegel RL, Kratzer TB, Giaquinto AN, Sung H, Jemal A. Cancer statistics, 2025. CA Cancer J Clin. 2025;75:10–45. [DOI] [PubMed] [PMC]

32.

Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022;72:7–33. [DOI] [PubMed]

33.

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65:5–29. [DOI] [PubMed]

34.

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68:7–30. [DOI] [PubMed]

35.

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019; 69:7–34. [DOI] [PubMed]

36.

Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023;73:17–48. [DOI] [PubMed]

37.

Kristen AV, Ajroud-Driss S, Conceição I, Gorevic P, Kyriakides T, Obici L. Patisiran, an RNAi therapeutic for the treatment of hereditary transthyretin-mediated amyloidosis. Neurodegener Dis Manag. 2019;9:5–23. [DOI] [PubMed]

38.

Zhang W, Jiang A, Jia BK, Jin Y, Chen Y, Li Z, et al. Progress in RNA-Targeted Therapeutics for Human Diseases. MedComm (2020). 2026;7:e70607. [DOI] [PubMed] [PMC]

39.

Lin H, Wang K, Xiong Y, Zhou L, Yang Y, Chen S, et al. Identification of Tumor Antigens and Immune Subtypes of Glioblastoma for mRNA Vaccine Development. Front Immunol. 2022;13:773264. [DOI] [PubMed] [PMC]

40.

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424. [DOI] [PubMed]

41.

Moore DC, Guinigundo AS. Biomarker-Driven Oncology Clinical Trials: Novel Designs in the Era of Precision Medicine. J Adv Pract Oncol. 2023;14:9–13. [DOI] [PubMed] [PMC]

42.

Ruiz-Garcia A, Baverel P, Bottino D, Dolton M, Feng Y, González-García I, et al. A comprehensive regulatory and industry review of modeling and simulation practices in oncology clinical drug development. J Pharmacokinet Pharmacodyn. 2023;50:147–72. [DOI] [PubMed] [PMC]

43.

Wong CH, Siah KW, Lo AW. Estimation of clinical trial success rates and related parameters. Biostatistics. 2019;20:273–86. [DOI] [PubMed] [PMC]

44.

Flaherty KT, Gray R, Chen A, Li S, Patton D, Hamilton SR, et al.; NCI-MATCH Team. The Molecular Analysis for Therapy Choice (NCI-MATCH) Trial: Lessons for Genomic Trial Design. J Natl Cancer Inst. 2020;112:1021–9. [DOI] [PubMed] [PMC]

45.

Alva AS, Mangat PK, Garrett-Mayer E, Halabi S, Hansra D, Calfa CJ, et al. Pembrolizumab in Patients With Metastatic Breast Cancer With High Tumor Mutational Burden: Results From the Targeted Agent and Profiling Utilization Registry (TAPUR) Study. J Clin Oncol. 2021;39:2443–51. [DOI] [PubMed]

46.

Ahn ER, Rothe M, Mangat PK, Garrett-Mayer E, Ali-Ahmad HM, Chan J, et al. Pertuzumab Plus Trastuzumab in Patients With Endometrial Cancer With ERBB2/3 Amplification, Overexpression, or Mutation: Results From the TAPUR Study. JCO Precis Oncol. 2023;7:e2200609. [DOI] [PubMed]

47.

Patel SP, Kurzrock R. PD-L1 Expression as a Predictive Biomarker in Cancer Immunotherapy. Mol Cancer Ther. 2015;14:847–56. [DOI] [PubMed]

48.

Lin X, Kang K, Chen P, Zeng Z, Li G, Xiong W, et al. Regulatory mechanisms of PD-1/PD-L1 in cancers. Mol Cancer. 2024;23:108. [DOI] [PubMed] [PMC]

49.

Casali PG, Abecassis N, Aro HT, Bauer S, Biagini R, Bielack S, et al.; ESMO Guidelines Committee and EURACAN. Soft tissue and visceral sarcomas: ESMO-EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018;29:iv51–67. [DOI] [PubMed]

50.

Blay JY, Casali P, Ray-Coquard I, Seckl MJ, Gietema J, de Herder WW, et al. Management of patients with rare adult solid cancers: objectives and evaluation of European reference networks (ERN) EURACAN. Lancet Reg Health Eur. 2024;39:100861. [DOI] [PubMed] [PMC]

51.

Mirzaei S, Mahabady MK, Zabolian A, Abbaspour A, Fallahzadeh P, Noori M, et al. Small interfering RNA (siRNA) to target genes and molecular pathways in glioblastoma therapy: Current status with an emphasis on delivery systems. Life Sci. 2021;275:119368. [DOI] [PubMed]

52.

Makowska M, Smolarz B, Romanowicz H. microRNAs (miRNAs) in Glioblastoma Multiforme (GBM)-Recent Literature Review. Int J Mol Sci. 2023;24:3521. [DOI] [PubMed] [PMC]

53.

Veeramachaneni RK, Suter RK, Rowland E, Jermakowicz A, Ayad NG. Glutaminase 2 as a therapeutic target in glioblastoma. Biochim Biophys Acta Rev Cancer. 2024;1879:189182. [DOI] [PubMed]

54.

Xiong Z, Raphael I, Olin M, Okada H, Li X, Kohanbash G. Glioblastoma vaccines: past, present, and opportunities. EBioMedicine. 2024;100:104963. [DOI] [PubMed] [PMC]

55.

Segura-Collar B, Hiller-Vallina S, de Dios O, Caamaño-Moreno M, Mondejar-Ruescas L, Sepulveda-Sanchez JM, et al. Advanced immunotherapies for glioblastoma: tumor neoantigen vaccines in combination with immunomodulators. Acta Neuropathol Commun. 2023;11:79. [DOI] [PubMed] [PMC]

56.

Mao XY, Dai JX, Zhou HH, Liu ZQ, Jin WL. Brain tumor modeling using the CRISPR/Cas9 system: state of the art and view to the future. Oncotarget. 2016;7:33461–71. [DOI] [PubMed] [PMC]

57.

Moure CJ, Diplas BH, Chen LH, Yang R, Pirozzi CJ, Wang Z, et al. CRISPR Editing of Mutant IDH1 R132H Induces a CpG Methylation-Low State in Patient-Derived Glioma Models of G-CIMP. Mol Cancer Res. 2019;17:2042–50. [DOI] [PubMed] [PMC]

58.

Zou Y, Sun X, Yang Q, Zheng M, Shimoni O, Ruan W, et al. Blood-brain barrier-penetrating single CRISPR-Cas9 nanocapsules for effective and safe glioblastoma gene therapy. Sci Adv. 2022;8:eabm8011. [DOI] [PubMed] [PMC]

59.

Yang Q, Zhou Y, Chen J, Huang N, Wang Z, Cheng Y. Gene Therapy for Drug-Resistant Glioblastoma via Lipid-Polymer Hybrid Nanoparticles Combined with Focused Ultrasound. Int J Nanomedicine. 2021;16:185–99. [DOI] [PubMed] [PMC]

60.

Kaban K, Hinterleitner C, Zhou Y, Salva E, Kantarci AG, Salih HR, et al. Therapeutic Silencing of BCL-2 Using NK Cell-Derived Exosomes as a Novel Therapeutic Approach in Breast Cancer. Cancers (Basel). 2021;13:2397. [DOI] [PubMed] [PMC]

61.

Ubanako P, Mirza S, Ruff P, Penny C. Exosome-mediated delivery of siRNA molecules in cancer therapy: triumphs and challenges. Front Mol Biosci. 2024;11:1447953. [DOI] [PubMed] [PMC]

62.

Subhan MA, Torchilin VP. Advances in siRNA Drug Delivery Strategies for Targeted TNBC Therapy. Bioengineering (Basel). 2024;11:830. [DOI] [PubMed] [PMC]

63.

Subhan MA, Filipczak N, Torchilin VP. Advances with Lipid-Based Nanosystems for siRNA Delivery to Breast Cancers. Pharmaceuticals (Basel). 2023;16:970. [DOI] [PubMed] [PMC]

64.

Chaiyawat P, Sangkhathat S, Chiangjong W, Wongtrakoongate P, Hongeng S, Pruksakorn D, et al. Targeting pediatric solid tumors in the new era of RNA therapeutics. Crit Rev Oncol Hematol. 2024;200:104406. [DOI] [PubMed]

65.

Sainero-Alcolado L, Sjöberg Bexelius T, Santopolo G, Yuan Y, Liaño-Pons J, Arsenian-Henriksson M. Defining neuroblastoma: From origin to precision medicine. Neuro Oncol. 2024;26:2174–92. [DOI] [PubMed] [PMC]

66.

Gregory GL, Copple IM. Modulating the expression of tumor suppressor genes using activating oligonucleotide technologies as a therapeutic approach in cancer. Mol Ther Nucleic Acids. 2022;31:211–23. [DOI] [PubMed] [PMC]

67.

Steurer M, Montillo M, Scarfò L, Mauro FR, Andel J, Wildner S, et al. Olaptesed pegol (NOX-A12) with bendamustine and rituximab: a phase IIa study in patients with relapsed/refractory chronic lymphocytic leukemia. Haematologica. 2019;104:2053–60. [DOI] [PubMed] [PMC]

68.

Schaible P, Bethge W, Lengerke C, Haraszti RA. RNA Therapeutics for Improving CAR T-cell Safety and Efficacy. Cancer Res. 2023;83:354–62. [DOI] [PubMed] [PMC]

69.

Xie N, Shen G, Gao W, Huang Z, Huang C, Fu L. Neoantigens: promising targets for cancer therapy. Signal Transduct Target Ther. 2023;8:9. [DOI] [PubMed] [PMC]

70.

JJACOB F, MONOD J. Genetic regulatory mechanisms in the synthesis of proteins. J Mol Biol. 1961;3:318–56. [DOI] [PubMed]

71.

Lee RC, Feinbaum RL, Ambros V. The C. Cell. 1993;75:843–54. [DOI] [PubMed]

72.

Lin H, Spradling AC. A novel group of pumilio mutations affects the asymmetric division of germline stem cells in the Drosophila ovary. Development. 1997;124:2463–76. [DOI] [PubMed]

73.

Brown CJ, Hendrich BD, Rupert JL, Lafrenière RG, Xing Y, Lawrence J, et al. The human XIST gene: analysis of a 17 kb inactive X-specific RNA that contains conserved repeats and is highly localized within the nucleus. Cell. 1992;71:527–42. [DOI] [PubMed]

74.

Bartolomei MS, Zemel S, Tilghman SM. Parental imprinting of the mouse H19 gene. Nature. 1991;351:153–5. [DOI] [PubMed]

75.

Brannan CI, Dees EC, Ingram RS, Tilghman SM. The product of the H19 gene may function as an RNA. Mol Cell Biol. 1990;10:28–36. [DOI] [PubMed] [PMC]

76.

Brown CJ, Ballabio A, Rupert JL, Lafreniere RG, Grompe M, Tonlorenzi R, et al. A gene from the region of the human X inactivation centre is expressed exclusively from the inactive X chromosome. Nature. 1991;349:38–44. [DOI] [PubMed]

77.

Salzman J, Gawad C, Wang PL, Lacayo N, Brown PO. Circular RNAs are the predominant transcript isoform from hundreds of human genes in diverse cell types. PLoS One. 2012;7:e30733. [DOI] [PubMed] [PMC]

78.

Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK, et al. Natural RNA circles function as efficient microRNA sponges. Nature. 2013;495:384–8. [DOI] [PubMed]

79.

Zamecnik PC, Stephenson ML. Inhibition of Rous sarcoma virus replication and cell transformation by a specific oligodeoxynucleotide. Proc Natl Acad Sci U S A. 1978;75:280–4. [DOI] [PubMed] [PMC]

80.

Stephenson ML, Zamecnik PC. Inhibition of Rous sarcoma viral RNA translation by a specific oligodeoxyribonucleotide. Proc Natl Acad Sci U S A. 1978;75:285–8. [DOI] [PubMed] [PMC]

81.

Roehr B. Fomivirsen approved for CMV retinitis. J Int Assoc Physicians AIDS Care. 1998;4:14–6. [PubMed]

82.

Gragoudas ES, Adamis AP, Cunningham ET Jr, Feinsod M, Guyer DR; VEGF Inhibition Study in Ocular Neovascularization Clinical Trial Group. Pegaptanib for neovascular age-related macular degeneration. N Engl J Med. 2004;351:2805–16. [DOI] [PubMed]

83.

Kaiser PK, Symons RCA, Shah SM, Quinlan EJ, Tabandeh H, Do DV, et al.; Sirna-027 Study Investigators. RNAi-based treatment for neovascular age-related macular degeneration by Sirna-027. Am J Ophthalmol. 2010;150:33–9.e2. [DOI] [PubMed]

84.

Mullard A. FDA approves landmark RNAi drug. Nat Rev Drug Discov. 2018;17:613. [DOI] [PubMed]

85.

Parums DV. Editorial: First Regulatory Approvals for CRISPR-Cas9 Therapeutic Gene Editing for Sickle Cell Disease and Transfusion-Dependent β-Thalassemia. Med Sci Monit. 2024;30:e944204. [DOI] [PubMed] [PMC]

86.

Biggs AT, Littlejohn LF. Describing mRNA Vaccine Technology for a Military Audience. Mil Med. 2023;188:547–54. [DOI] [PubMed]

87.

Demongeot J, Fougère C. mRNA COVID-19 Vaccines-Facts and Hypotheses on Fragmentation and Encapsulation. Vaccines (Basel). 2022;11:40. [DOI] [PubMed] [PMC]

88.

Gregoriadis G. Drug entrapment in liposomes. FEBS Lett. 1973;36:292–6. [DOI] [PubMed]

89.

Gregoriadis G, Ryman BE. Liposomes as carriers of enzymes or drugs: a new approach to the treatment of storage diseases. Biochem J. 1971;124:58P. [DOI] [PubMed] [PMC]

90.

Leung AK, Tam YY, Cullis PR. Lipid nanoparticles for short interfering RNA delivery. Adv Genet. 2014;88:71–110. [DOI] [PubMed] [PMC]

91.

Choung S, Kim YJ, Kim S, Park HO, Choi YC. Chemical modification of siRNAs to improve serum stability without loss of efficacy. Biochem Biophys Res Commun. 2006;342:919–27. [DOI] [PubMed]

92.

Wei PS, Thota N, John G, Chang E, Lee S, Wang Y, et al. Enhancing RNA-lipid nanoparticle delivery: Organ- and cell-specificity and barcoding strategies. J Control Release. 2024;375:366–88. [DOI] [PubMed] [PMC]

93.

Honor A, Rudnick SR, Bonkovsky HL. Givosiran to treat acute porphyria. Drugs Today (Barc). 2021;57:47–59. [DOI] [PubMed]

94.

Syed YY. Nedosiran: First Approval. Drugs. 2023;83:1729–33. [DOI] [PubMed] [PMC]

95.

Łusakowska A, Wójcik A, Frączek A, Aragon-Gawińska K, Potulska-Chromik A, Baranowski P, et al. Long-term nusinersen treatment across a wide spectrum of spinal muscular atrophy severity: a real-world experience. Orphanet J Rare Dis. 2023;18:230. [DOI] [PubMed] [PMC]

96.

Urits I, Swanson D, Swett MC, Patel A, Berardino K, Amgalan A, et al. A Review of Patisiran (ONPATTRO^®) for the Treatment of Polyneuropathy in People with Hereditary Transthyretin Amyloidosis. Neurol Ther. 2020;9:301–15. [DOI] [PubMed] [PMC]

97.

Karimi MA, Esmaeilpour Moallem F, Gholami Chahkand MS, Azarm E, Emami Kazemabad MJ, Dadkhah PA. Assessing the effectiveness and safety of Patisiran and Vutrisiran in ATTRv amyloidosis with polyneuropathy: a systematic review. Front Neurol. 2024;15:1465747. [DOI] [PubMed] [PMC]

98.

Sardh E, Balwani M, Rees DC, Anderson KE, Jia G, Sweetser MT, et al. Long-term follow-up of givosiran treatment in patients with acute intermittent porphyria from a phase 1/2, 48-month open-label extension study. Orphanet J Rare Dis. 2024;19:365. [DOI] [PubMed] [PMC]

99.

Scott LJ, Keam SJ. Lumasiran: First Approval. Drugs. 2021;81:277–82. [DOI] [PubMed]

100.

Shirley M. Casimersen: First Approval. Drugs. 2021;81:875–879. [DOI] [PubMed]

101.

Mok CKP, Tang YS, Tan CW, Chong KC, Chen C, Sun Y, et al. Comparison of safety and immunogenicity in the elderly after receiving either Comirnaty or Spikevax monovalent XBB1.5 COVID-19 vaccine. J Infect. 2025;90:106374. [DOI] [PubMed]

102.

Liu C, Shi Q, Huang X, Koo S, Kong N, Tao W. mRNA-based cancer therapeutics. Nat Rev Cancer. 2023;23:526–543. [DOI] [PubMed]

103.

Gawalski K, Przybyszewska W, Hunia J, Gawalska A, Rymarz A. Unraveling the potential: mRNA therapeutics in oncology. Front Oncol. 2025;15:1643444. [DOI] [PubMed] [PMC]

104.

Clinical advances and ongoing trials on mRNA vaccines for cancer treatment. Clinical advances and ongoing trials on mRNA vaccines for cancer treatment. Lancet Oncol. 2022;23:e450–8. [DOI] [PubMed] [PMC]

105.

Tiwade PB, Fung V, VanKeulen-Miller R, Narasipura EA, Ma Y, Fenton OS. Non-Viral RNA Therapies for Non-Small Cell Lung Cancer and Their Corresponding Clinical Trials. Mol Pharm. 2025;22:1752–74. [DOI] [PubMed]

106.

Grillone K, Caridà G, Luciano F, Cordua A, Di Martino MT, Tagliaferri P, et al. A systematic review of non-coding RNA therapeutics in early clinical trials: a new perspective against cancer. J Transl Med. 2024;22:731. [DOI] [PubMed] [PMC]

107.

Coan M, Haefliger S, Ounzain S, Johnson R. Targeting and engineering long non-coding RNAs for cancer therapy. Nat Rev Genet. 2024;25:578–95. [DOI] [PubMed]

108.

Uppaluri KR, Challa HJ, Gaur A, Jain R, Krishna Vardhani K, Geddam A, et al. Unlocking the potential of non-coding RNAs in cancer research and therapy. Transl Oncol. 2023;35:101730. [DOI] [PubMed] [PMC]

109.

Winkle M, El-Daly SM, Fabbri M, Calin GA. Noncoding RNA therapeutics—challenges and potential solutions. Nat Rev Drug Discov. 2021;20:629–51. [DOI] [PubMed] [PMC]

110.

Kara G, Calin GA, Ozpolat B. RNAi-based therapeutics and tumor targeted delivery in cancer. Adv Drug Deliv Rev. 2022;182:114113. [DOI] [PubMed]

111.

Yan Y, Liu S, Wen J, He Y, Duan C, Nabavi N, et al. Advances in RNA-based cancer therapeutics: pre-clinical and clinical implications. Mol Cancer. 2025;24:251. [DOI] [PubMed] [PMC]

112.

Yang X, Liang Y, Tong S. Advancing cancer treatment: in vivo delivery of therapeutic small noncoding RNAs. Front Mol Biosci. 2024;10:1297413. [DOI] [PubMed] [PMC]

113.

Seyhan AA. Trials and Tribulations of MicroRNA Therapeutics. Int J Mol Sci. 2024;25:1469. [DOI] [PubMed] [PMC]

114.

Ito M, Miyata Y, Okada M. Current clinical trials with non-coding RNA-based therapeutics in malignant diseases: A systematic review. Transl Oncol. 2023;31:101634. [DOI] [PubMed] [PMC]

115.

Wu D, Hu L, Wang X, Yu Y, Jia SP, Huang HY, et al. Clinical development of mRNA therapies against solid tumors. J Hematol Oncol. 2023;16:75. [DOI] [PubMed] [PMC]

116.

Chi WY, Hu Y, Huang HC, Kuo HH, Lin SH, Kuo CJ, et al. Molecular targets and strategies in the development of nucleic acid cancer vaccines: from shared to personalized antigens. J Biomed Sci. 2024;31:94. [DOI] [PubMed] [PMC]

117.

Weber JS, Carlino MS, Khattak A, Meniawy T, Ansstas G, Taylor MH, et al. Individualised neoantigen therapy mRNA-4157 (V940) plus pembrolizumab versus pembrolizumab monotherapy in resected melanoma (KEYNOTE-942): a randomised, phase 2b study. Lancet. 2024;403:632–44. [DOI] [PubMed]

118.

Rojas LA, Sethna Z, Soares KC, Olcese C, Pang N, Patterson E, et al. Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer. Nature. 2023;618:144–50. [DOI] [PubMed] [PMC]

119.

Kong B, Kim Y, Kim EH, Suk JS, Yang Y. mRNA: A promising platform for cancer immunotherapy. Adv Drug Deliv Rev. 2023;199:114993. [DOI] [PubMed] [PMC]

120.

Gao Y, Yang L, Li Z, Peng X, Li H. mRNA vaccines in tumor targeted therapy: mechanism, clinical application, and development trends. Biomark Res. 2024;12:93. [DOI] [PubMed] [PMC]

121.

Huang R, Du H, Cheng L, Zhang P, Meng F, Zhong Z. Targeted nanodelivery of siRNA against KRAS G12D inhibits pancreatic cancer. Acta Biomater. 2023;168:529–39. [DOI] [PubMed]

122.

Shirvan M, Racheli M, Yaron M, Zorde E, ShragaiO, Maor Aloni R, et al. SIL-204 siRNA encapsulated in extended release microparticles for the treatment of localized cancer that harbors a KRAS G12x or G13D mutation. J Clin Oncol. 2025;43:745. [DOI]

123.

Xiao K, Lai Y, Yuan W, Li S, Liu X, Xiao Z, et al. mRNA-based chimeric antigen receptor T cell therapy: Basic principles, recent advances and future directions. Interdiscip Med. 2024;2:e20230036. [DOI]

124.

Wu J, Wu W, Zhou B, Li B. Chimeric antigen receptor therapy meets mRNA technology. Trends Biotechnol. 2024;42:228–40. [DOI] [PubMed]

125.

Kitte R, Rabel M, Geczy R, Park S, Fricke S, Koehl U, et al. Lipid nanoparticles outperform electroporation in mRNA-based CAR T cell engineering. Mol Ther Methods Clin Dev. 2023;31:101139. [DOI] [PubMed] [PMC]

126.

Pacesa M, Pelea O, Jinek M. Past, present, and future of CRISPR genome editing technologies. Cell. 2024;187:1076–100. [DOI] [PubMed]

127.

Zhu G, Zhou X, Wen M, Qiao J, Li G, Yao Y. CRISPR-Cas13: Pioneering RNA Editing for Nucleic Acid Therapeutics. Biodes Res. 2024;6:0041. [DOI] [PubMed] [PMC]

128.

Wang S, Weissman D, Dong Y. RNA chemistry and therapeutics. Nat Rev Drug Discov. 2025;24:828–51. [DOI] [PubMed] [PMC]

129.

Naeem S, Zhang J, Zhang Y, Wang Y. Nucleic acid therapeutics: Past, present, and future. Mol Ther Nucleic Acids. 2024;36:102440. [DOI] [PubMed] [PMC]

130.

Zhang L, Wei J, Zou Z, He C. RNA modification systems as therapeutic targets. Nat Rev Drug Discov. 2026;25:59–78. [DOI] [PubMed]

131.

O’Leary E, Jiang Y, Kristensen LS, Hansen TB, Kjems J. The therapeutic potential of circular RNAs. Nat Rev Genet. 2025;26:230–44. [DOI] [PubMed]

132.

Whitley J, Zwolinski C, Denis C, Maughan M, Hayles L, Clarke D, et al. Development of mRNA manufacturing for vaccines and therapeutics: mRNA platform requirements and development of a scalable production process to support early phase clinical trials. Transl Res. 2022;242:38–55. [DOI] [PubMed] [PMC]

133.

Hengelbrock A, Schmidt A, Helgers H, Vetter FL, Strube J. Scalable mRNA Machine for Regulatory Approval of Variable Scale between 1000 Clinical Doses to 10 Million Manufacturing Scale Doses. Processes. 2023;11:745. [DOI]

134.

Ho LLY, Schiess GHA, Miranda P, Weber G, Astakhova K. Pseudouridine and N 1-methylpseudouridine as potent nucleotide analogues for RNA therapy and vaccine development. RSC Chem Biol. 2024;5:418–25. [DOI] [PubMed] [PMC]

135.

Driscoll J, Gondaliya P, Zinn DA, Jain R, Yan IK, Dong H, et al. Using aptamers for targeted delivery of RNA therapies. Mol Ther. 2025;33:1344–67. [DOI] [PubMed] [PMC]

136.

Nabih NW, Hassan HAFM, Preis E, Schaefer J, Babker A, Abbas AM, et al. Antibody-functionalized lipid nanocarriers for RNA-based cancer gene therapy: advances and challenges in targeted delivery. Nanoscale Adv. 2025;7:5905–31. [DOI] [PubMed] [PMC]

137.

Brown DG, Wobst HJ, Kapoor A, Kenna LA, Southall N. Clinical development times for innovative drugs. Nat Rev Drug Discov. 2022;21:793–4. [DOI] [PubMed] [PMC]