Abstract
Nucleic acid therapeutics are emerging as transformative agents in antiviral treatment, leveraging precise genetic interventions to combat viral infections. This mini-review examines key modalities including Antisense Oligonucleotides (ASOs), Small Interfering RNAs (siRNAs), CRISPR-based gene editing, and mRNA vaccines. These approaches utilize cellular mechanisms to inhibit viral replication and offer targeted gene silencing, crucial for addressing rapidly mutating viruses. The review highlights advancements in delivery systems, particularly lipid nanoparticles, and discusses the clinical potential and challenges of these therapies, such as safety concerns related to immune responses and genotoxicity. It also underscores the rapid development and effectiveness of mRNA vaccines demonstrated during the COVID-19 pandemic, reflecting the adaptability and potential of nucleic acid therapies. The review calls for continued innovation and multidisciplinary research to enhance the efficacy, safety, and clinical application of these promising antiviral strategies.
Keywords:
Nucleic acid therapeutics, CRISPR, antisense oligonucleotides, lipid nanoparticles, small Interfering RNAReferences
1. Rintz E, Celik B, Fnu N, Herreno-Pachon AM, Khan S, Benincore-Florez E, et al. Molecular therapy and nucleic acid adeno-associated virus-based gene therapy delivering combinations of two growth-associated genes to MPS IVA mice. Mol Ther Nucleic Acids. 2024;35(2):102211.
2. Domingues W, Folgosi VA, Sanabani SS, Leite Junior PD, Assone T, Casseb J. Novel approaches for HTLV-1 therapy: innovative applications of CRISPR-Cas9. Rev Inst Med Trop Sao Paulo. 2024;66:e48.
3. Lu T, Zhang C, Li Z, Wei Y, Sadewasser A, Yan Y, et al. Human angiotensin-converting enzyme 2-specific antisense oligonucleotides reduce infection with SARS-CoV-2 variants. J Allergy Clin Immunol. 2024.154(4):1044-1059.
4. Kang H, Ga YJ, Kim SH, Cho YH, Kim JW, Kim C, et al. Small interfering RNA (siRNA)-based therapeutic applications against viruses: principles, potential, and challenges. J Biomed Sci. 2023;30(1):88.
5. Nair DM, Vajravelu LK, Thulukanam J, Paneerselvam V, Vimala PB, Lathakumari RH. Tackling hepatitis B Virus with CRISPR/Cas9: advances, challenges, and delivery strategies. Virus Genes. 2024.60(6):592-602.
6. Wu Z, Sun W, Qi H. Recent Advancements in mRNA Vaccines: From Target Selection to Delivery Systems. Vaccines (Basel). 2024;12(8).
7. Zhang M, Chen H, Liu H, Tang H. The impact of integrated hepatitis B virus DNA on oncogenesis and antiviral therapy. Biomark Res. 2024;12(1):84.
8. Srivastava S, Kumar S, Ashique S, Sridhar SB, Shareef J, Thomas S. Novel antiviral approaches for Marburg: a promising therapeutics in the pipeline. Front Microbiol. 2024;15:1387628.
9. Coldbeck-Shackley RC, Adamson PJ, Whybrow D, Selway CA, Papanicolas LE, Turra M, et al. Direct whole-genome sequencing of HIV-1 for clinical drug-resistance analysis and public health surveillance. J Clin Virol. 2024;174:105709.
10. Wang J, Tan M, Wang Y, Liu X, Lin A. Advances in modification and delivery of nucleic acid drugs. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2023;52(4):417-28.
11. Smith A, Zhang I, Trang P, Liu F. Engineering of RNase P Ribozymes for Therapy against Human Cytomegalovirus Infection. Viruses. 2024;16(8).
12. Dai J, Jiang X, da Silva-Junior EF, Du S, Liu X, Zhan P. Recent advances in the molecular design and applications of viral RNA-targeting antiviral modalities. Drug Discov Today. 2024;29(8):104074.
13. Chen S, Heendeniya SN, Le BT, Rahimizadeh K, Rabiee N, Zahra Qua, et al. Splice-Modulating Antisense Oligonucleotides as Therapeutics for Inherited Metabolic Diseases. BioDrugs. 2024;38(2):177-203.
14. Lauffer MC, van Roon-Mom W, Aartsma-Rus A, N = C. Possibilities and limitations of antisense oligonucleotide therapies for the treatment of monogenic disorders. Communications Medicine. 2024;4(1):6.
15. Collotta D, Bertocchi I, Chiapello E, Collino M. Antisense oligonucleotides: a novel Frontier in pharmacological strategy. Front Pharmacol. 2023;14:1304342.
16. Rogalska ME, Vivori C, Valcárcel J. Regulation of pre-mRNA splicing: roles in physiology and disease, and therapeutic prospects. Nature Reviews Genetics. 2023;24(4):251-69.
17. Makhmudova U, Steinhagen-Thiessen E, Volpe M, Landmesser U. Advances in nucleic acid-targeted therapies for cardiovascular disease prevention. Cardiovasc Res. 2024;120(10):1107-25.
18. Ersöz E, Demir‐Dora D. Unveiling the potential of antisense oligonucleotides: Mechanisms, therapies, and safety insights. Drug Development Research. 2024;85(4):e22187.
19. Dauksaite V, Tas A, Wachowius F, Spruit A, van Hemert MJ, Snijder EJ, et al. Highly Potent Antisense Oligonucleotides Locked Nucleic Acid Gapmers Targeting the SARS-CoV-2 RNA Genome. Nucleic Acid Ther. 2023;33(6):381-5.
20. Rook ME, Southwell AL. Antisense Oligonucleotide Therapy: From Design to the Huntington Disease Clinic. BioDrugs. 2022;36(2):105-19.
21. Nakamura A, Ali SA, Kapoor M. Antisense oligonucleotide-based therapies for the treatment of osteoarthritis: Opportunities and roadblocks. Bone. 2020;138:115461.
22. Li Q, Dong M, Chen P. Advances in structural-guided modifications of siRNA. Bioorg Med Chem. 2024;110:117825.
23. Alshaer W, Zureigat H, Al Karaki A, Al-Kadash A, Gharaibeh L, Hatmal MmM, et al. siRNA: Mechanism of action, challenges, and therapeutic approaches. European Journal of Pharmacology. 2021;905:174178.
24. Gonzalez RD, Simoes S, Ferreira L, Carvalho ATP. Designing Cell Delivery Peptides and SARS-CoV-2-Targeting Small Interfering RNAs: A Comprehensive Bioinformatics Study with Generative Adversarial Network-Based Peptide Design and In Vitro Assays. Mol Pharm. 2023;20(12):6079-89.
25. He A, Huang Z, Feng Q, Zhang S, Li F, Li D, et al. AC099850.3 promotes HBV-HCC cell proliferation and invasion through regulating CD276: a novel strategy for sorafenib and immune checkpoint combination therapy. J Transl Med. 2024;22(1):809.
26. Chatterjee K, Lakdawala S, Quadir SS, Puri D, Mishra DK, Joshi G, et al. siRNA-Based Novel Therapeutic Strategies to Improve Effectiveness of Antivirals: An Insight. AAPS PharmSciTech. 2023;24(6):170.
27. Cisneros E, Sherwani N, Lanier OL, Peppas NA. Targeted delivery methods for RNA interference are necessary to obtain a potential functional cure for HIV/AIDS. Adv Drug Deliv Rev. 2023;199:114970.
28. Kick L, Kirchner M, Schneider S. CRISPR-Cas9: From a bacterial immune system to genome-edited human cells in clinical trials. Bioengineered. 2017;8(3):280-6.
29. Aljabali AAA, El-Tanani M, Tambuwala MM. Principles of CRISPR-Cas9 technology: Advancements in genome editing and emerging trends in drug delivery. Journal of Drug Delivery Science and Technology. 2024;92:105338.
30. Liu S-C, Feng Y-L, Sun X-N, Chen R-D, Liu Q, Xiao J-J, et al. Target residence of Cas9-sgRNA influences DNA double-strand break repair pathway choices in CRISPR/Cas9 genome editing. Genome Biology. 2022;23(1):165.
31. Hu Q, Espejo Valle-Inclan J, Dahiya R, Guyer A, Mazzagatti A, Maurais EG, et al. Non-homologous end joining shapes the genomic rearrangement landscape of chromothripsis from mitotic errors. Nat Commun. 2024;15(1):5611.
32. Xue C, Greene EC. DNA Repair Pathway Choices in CRISPR-Cas9-Mediated Genome Editing. Trends Genet. 2021;37(7):639-56.
33. Dash PK, Chen C, Kaminski R, Su H, Mancuso P, Sillman B, et al. CRISPR editing of CCR5 and HIV-1 facilitates viral elimination in antiretroviral drug-suppressed virus-infected humanized mice. Proc Natl Acad Sci U S A. 2023;120(19):e2217887120.
34. Badu P, Baniulyte G, Sammons MA, Pager CT. Activation of ATF3 via the integrated stress response pathway regulates innate immune response to restrict Zika virus. J Virol. 2024:e0105524.
35. Hsieh MJ, Tsai PH, Chiang PH, Kao ZK, Zhuang ZQ, Hsieh AR, et al. Genomic insights into mRNA COVID-19 vaccines efficacy: Linking genetic polymorphisms to waning immunity. Hum Vaccin Immunother. 2024;20(1):2399382.
36. Kumar V, Soni M, Dutt M. Assessing the incidence of myocarditis risk in mRNA COVID-19 vaccines: a systematic review and meta-analysis. The Evidence. 2024;2(1).
37. Tang X, Zhang J, Sui D, Xu Z, Yang Q, Wang T, et al. Durable protective efficiency provide by mRNA vaccines require robust immune memory to antigens and weak immune memory to lipid nanoparticles. Mater Today Bio. 2024;25:100988.
38. Jamous YF, Alhomoud DA. The Safety and Effectiveness of mRNA Vaccines Against SARS-CoV-2. Cureus. 2023;15(9):e45602.
39. Lu RM, Hsu HE, Perez S, Kumari M, Chen GH, Hong MH, et al. Current landscape of mRNA technologies and delivery systems for new modality therapeutics. J Biomed Sci. 2024;31(1):89.
40. Qi S, Zhang X, Yu X, Jin L, Yang K, Wang Y, et al. Supramolecular Lipid Nanoparticles Based on Host-Guest Recognition: A New Generation Delivery System of mRNA Vaccines For Cancer Immunotherapy. Adv Mater. 2024;36(23):e2311574.
41. Mohammadian Farsani A, Mokhtari N, Nooraei S, Bahrulolum H, Akbari A, Farsani ZM, et al. Lipid nanoparticles: The game-changer in CRISPR-Cas9 genome editing. Heliyon. 2024;10(2):e24606.
42. Lee H, You G, Yeo S, Lee H, Mok H. Effects of Histidine Oligomers in Lipid Nanoparticles on siRNA Delivery. Macromol Biosci. 2024;24(8):e2400043.
43. Wang J, Zhang Y, Dong S, Zha W, Liu C, Wang Y, et al. Bivalent mRNA vaccines against three SARS-CoV-2 variants mediated by new ionizable lipid nanoparticles. Int J Pharm. 2023;642:123155.
44. Im SH, Jang M, Park JH, Chung HJ. Finely tuned ionizable lipid nanoparticles for CRISPR/Cas9 ribonucleoprotein delivery and gene editing. J Nanobiotechnology. 2024;22(1):175.
45. Kasiewicz LN, Biswas S, Beach A, Ren H, Dutta C, Mazzola AM, et al. GalNAc-Lipid nanoparticles enable non-LDLR dependent hepatic delivery of a CRISPR base editing therapy. Nat Commun. 2023;14(1):2776.
46. Farzanehpour M, Miri A, Alvanegh AG, Gouvarchinghaleh HE. Viral Vectors, Exosomes, and Vexosomes: Potential armamentarium for delivering CRISPR/Cas to cancer cells. Biochem Pharmacol. 2023;212:115555.
47. Wang J-H, Gessler DJ, Zhan W, Gallagher TL, Gao G. Adeno-associated virus as a delivery vector for gene therapy of human diseases. Signal Transduction and Targeted Therapy. 2024;9(1):78.
48. Ahmadi SE, Soleymani M, Shahriyary F, Amirzargar MR, Ofoghi M, Fattahi MD, et al. Viral vectors and extracellular vesicles: innate delivery systems utilized in CRISPR/Cas-mediated cancer therapy. Cancer Gene Ther. 2023;30(7):936-54.
49. Ying M, Wang H, Liu T, Han Z, Lin K, Shi Q, et al. CLEAR Strategy Inhibited HSV Proliferation Using Viral Vectors Delivered CRISPR-Cas9. Pathogens. 2023;12(6).
50. Dobrowsky T, Gianni D, Pieracci J, Suh J. AAV manufacturing for clinical use: Insights on current challenges from the upstream process perspective. Current Opinion in Biomedical Engineering. 2021;20:100353.
51. Zhang L, Lou W, Wang J. Advances in nucleic acid therapeutics: structures, delivery systems, and future perspectives in cancer treatment. Clin Exp Med. 2024;24(1):200.
52. Corey DR, Damha MJ, Manoharan M. Challenges and Opportunities for Nucleic Acid Therapeutics. Nucleic Acid Ther. 2022;32(1):8-13.
53. LaBauve AE, Saada EA, Jones IKA, Mosesso R, Noureddine A, Techel J, et al. Lipid-coated mesoporous silica nanoparticles for anti-viral applications via delivery of CRISPR-Cas9 ribonucleoproteins. Sci Rep. 2023;13(1):6873.
54. Modell AE, Lim D, Nguyen TM, Sreekanth V, Choudhary A. CRISPR-based therapeutics: current challenges and future applications. Trends Pharmacol Sci. 2022;43(2):151-61.
55. Quazi S. Artificial intelligence and machine learning in precision and genomic medicine. Med Oncol. 2022;39(8):120.
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Copyright (c) 2025 Senthil Thirusangu, Janet Prameela Dsouza, Sumana Mukhopadhyay, Abdullahi Saminu, Tathagata Jha, Prabhat, Aroop Mohanty
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