Nonviral Delivery Systems for Antisense Oligonucleotide Therapeutics

Overview

Journal Biomater Res

Specialty Biomedical Engineering

Date 2022 Sep 30

PMID 36180936

Authors

Si Huang

Xin-Yan Hao

Yong-Jiang Li

Jun-Yong Wu

Da-Xiong Xiang

Shilin Luo

Affiliations

Soon will be listed here.

Abstract

Antisense oligonucleotides (ASOs) are an important tool for the treatment of many genetic disorders. However, similar to other gene drugs, vectors are often required to protect them from degradation and clearance, and to accomplish their transport in vivo. Compared with viral vectors, artificial nonviral nanoparticles have a variety of design, synthesis, and formulation possibilities that can be selected to accomplish protection and delivery for specific applications, and they have served critical therapeutic purposes in animal model research and clinical applications, allowing safe and efficient gene delivery processes into the target cells. We believe that as new ASO drugs develop, the exploration for corresponding nonviral vectors is inevitable. Intensive development of nonviral vectors with improved delivery strategies based on specific targets can continue to expand the value of ASO therapeutic approaches. Here, we provide an overview of current nonviral delivery strategies, including ASOs modifications, action mechanisms, and multi-carrier methods, which aim to address the irreplaceable role of nonviral vectors in the progressive development of ASOs delivery.

Citing Articles

Exploring precision treatments in immune-mediated inflammatory diseases: Harnessing the infinite potential of nucleic acid delivery.

Xu L, Shao Z, Fang X, Xin Z, Zhao S, Zhang H Exploration (Beijing). 2025; 5(1):20230165.

PMID: 40040830 PMC: 11875455. DOI: 10.1002/EXP.20230165.

Integrating Machine Learning-Based Approaches into the Design of ASO Therapies.

Leckie J, Yokota T Genes (Basel). 2025; 16(2).

PMID: 40004514 PMC: 11855077. DOI: 10.3390/genes16020185.

Multifunctional molecular hybrid for targeted colorectal cancer cells: Integrating doxorubicin, AS1411 aptamer, and T9/U4 ASO.

Jiramitmongkon K, Rotkrua P, Khanchaitit P, Arunpanichlert J, Soontornworajit B PLoS One. 2025; 20(2):e0317559.

PMID: 39946362 PMC: 11825018. DOI: 10.1371/journal.pone.0317559.

Photochemical Stabilization of Self-Assembled Spherical Nucleic Acids.

Kaviani S, Bai H, Das T, Asohan J, Elmanzalawy A, Marlyn J Small. 2025; 21(7):e2407742.

PMID: 39790078 PMC: 11840461. DOI: 10.1002/smll.202407742.

Endosomal Escape and Nuclear Localization: Critical Barriers for Therapeutic Nucleic Acids.

Allen R, Yokota T Molecules. 2025; 29(24.

PMID: 39770086 PMC: 11677605. DOI: 10.3390/molecules29245997.

References

Yin W, Rogge M . Targeting RNA: A Transformative Therapeutic Strategy. Clin Transl Sci. 2019; 12(2):98-112. PMC: 6440575. DOI: 10.1111/cts.12624. View

Wang H, Ding S, Zhang Z, Wang L, You Y . Cationic micelle: A promising nanocarrier for gene delivery with high transfection efficiency. J Gene Med. 2019; 21(7):e3101. DOI: 10.1002/jgm.3101. View

Huang L, Low A, Damle S, Keenan M, Kuntz S, Murray S . Antisense suppression of the nonsense mediated decay factor Upf3b as a potential treatment for diseases caused by nonsense mutations. Genome Biol. 2018; 19(1):4. PMC: 5769327. DOI: 10.1186/s13059-017-1386-9. View

Kay E, Stulz R, Becquart C, Lovric J, Tangemo C, Thomen A . NanoSIMS Imaging Reveals the Impact of Ligand-ASO Conjugate Stability on ASO Subcellular Distribution. Pharmaceutics. 2022; 14(2). PMC: 8876276. DOI: 10.3390/pharmaceutics14020463. View

Chen Y, Huang Y, Huang H, Luo Z, Zhang Z, Sun R . Farnesylthiosalicylic acid-derivatized PEI-based nanocomplex for improved tumor vaccination. Mol Ther Nucleic Acids. 2021; 26:594-602. PMC: 8517092. DOI: 10.1016/j.omtn.2021.09.006. View

Atkin-Smith G, Poon I . Disassembly of the Dying: Mechanisms and Functions. Trends Cell Biol. 2016; 27(2):151-162. DOI: 10.1016/j.tcb.2016.08.011. View

Karlsson J, Rhodes K, Green J, Tzeng S . Poly(beta-amino ester)s as gene delivery vehicles: challenges and opportunities. Expert Opin Drug Deliv. 2020; 17(10):1395-1410. PMC: 7658038. DOI: 10.1080/17425247.2020.1796628. View

Yu R, Gunawan R, Post N, Zanardi T, Hall S, Burkey J . Disposition and Pharmacokinetics of a GalNAc3-Conjugated Antisense Oligonucleotide Targeting Human Lipoprotein (a) in Monkeys. Nucleic Acid Ther. 2016; 26(6):372-380. DOI: 10.1089/nat.2016.0623. View

Xu C, Iqbal S, Shen S, Luo Y, Yang X, Wang J . Development of "CLAN" Nanomedicine for Nucleic Acid Therapeutics. Small. 2019; 15(16):e1900055. DOI: 10.1002/smll.201900055. View

10.

Beha M, Ryu J, Kim Y, Chung H . Delivery of antisense oligonucleotides using multi-layer coated gold nanoparticles to methicillin-resistant S. aureus for combinatorial treatment. Mater Sci Eng C Mater Biol Appl. 2021; 126:112167. DOI: 10.1016/j.msec.2021.112167. View

11.

Somiya M, Kuroda S . Development of a virus-mimicking nanocarrier for drug delivery systems: The bio-nanocapsule. Adv Drug Deliv Rev. 2015; 95:77-89. DOI: 10.1016/j.addr.2015.10.003. View

12.

Harloff-Helleberg S, Nielsen L, Nielsen H . Animal models for evaluation of oral delivery of biopharmaceuticals. J Control Release. 2017; 268:57-71. DOI: 10.1016/j.jconrel.2017.09.025. View

13.

Radchatawedchakoon W, Krajarng A, Niyomtham N, Watanapokasin R, Yingyongnarongkul B . High transfection efficiency of cationic lipids with asymmetric acyl-cholesteryl hydrophobic tails. Chemistry. 2011; 17(11):3287-95. DOI: 10.1002/chem.201001622. View

14.

Chen L, Li G, Wang X, Li J, Zhang Y . Spherical Nucleic Acids for Near-Infrared Light-Responsive Self-Delivery of Small-Interfering RNA and Antisense Oligonucleotide. ACS Nano. 2021; 15(7):11929-11939. DOI: 10.1021/acsnano.1c03072. View

15.

Alphandery E . Natural Metallic Nanoparticles for Application in Nano-Oncology. Int J Mol Sci. 2020; 21(12). PMC: 7352233. DOI: 10.3390/ijms21124412. View

16.

Lamichhane T, Raiker R, Jay S . Exogenous DNA Loading into Extracellular Vesicles via Electroporation is Size-Dependent and Enables Limited Gene Delivery. Mol Pharm. 2015; 12(10):3650-7. PMC: 4826735. DOI: 10.1021/acs.molpharmaceut.5b00364. View

17.

Budnik V, Ruiz-Canada C, Wendler F . Extracellular vesicles round off communication in the nervous system. Nat Rev Neurosci. 2016; 17(3):160-72. PMC: 4989863. DOI: 10.1038/nrn.2015.29. View

18.

Bobo D, Robinson K, Islam J, Thurecht K, Corrie S . Nanoparticle-Based Medicines: A Review of FDA-Approved Materials and Clinical Trials to Date. Pharm Res. 2016; 33(10):2373-87. DOI: 10.1007/s11095-016-1958-5. View

19.

Kauffman A, Piotrowski-Daspit A, Nakazawa K, Jiang Y, Datye A, Saltzman W . Tunability of Biodegradable Poly(amine- co-ester) Polymers for Customized Nucleic Acid Delivery and Other Biomedical Applications. Biomacromolecules. 2018; 19(9):3861-3873. PMC: 6510397. DOI: 10.1021/acs.biomac.8b00997. View

20.

Zhu C, Jung S, Meng F, Zhu X, Park T, Zhong Z . Reduction-responsive cationic biodegradable micelles based on PDMAEMA-SS-PCL-SS-PDMAEMA triblock copolymers for gene delivery. J Control Release. 2011; 152 Suppl 1:e188-90. DOI: 10.1016/j.jconrel.2011.08.081. View