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Oligonucleotide therapeutics and their chemical modification strategies for clinical applications

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Abstract

Background

Oligonucleotide therapeutics have emerged as a promising and dynamic class of pharmaceutical agents with remarkable potential for treating a wide spectrum of genetic and acquired diseases. These therapeutic entities, comprising short nucleic acid sequences of either ribonucleic acids (RNA) or deoxyribonucleic acids (DNA), offer the distinct advantage of precise targeting and the ability to interfere with disease-causing genes or proteins. Despite their inherent therapeutic potential, their clinical utility has been hampered by various challenges, including rapid degradation, limited cellular uptake, and unintended immune responses.

Area covered

Chemical modification strategies have been extensively explored to overcome these limitations and enhance their pharmacological properties. In this review, we provide a comprehensive overview of oligonucleotide therapeutics and their associated chemical modification approaches, highlighting their potential in the clinical realm.

Expert opinion

By elucidating the progress made in chemical modifications and their implications for clinical translation, we seek to highlight the pivotal role of these strategies in realizing the full therapeutic potential of oligonucleotide-based therapies for treating a wide range of diseases.

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Acknowledgements

This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT) (No. 2018R1A5A2025286, 2022M3E5F1081328, RS-2023-00261343), the Ministry of Science & ICT (No. 2022M3A9H1014125), and the Korean government (Ministry of Food and Drug Safety) (No. 22203MFDS405).

Funding

Korea Health Industry Development Institute,22203MFDS405, Hyukjin Lee, National Research Foundation(NRF), 2018R1A5A2025286, Hyukjin Lee, 2022M3E5F1081328, Hyukjin Lee,National Research Foundation (NRF), RS-2023-00261343, Hyukjin Lee, 2022M3A9H1014125, Hyukjin Lee.

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  1. College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, 03760, Republic of Korea

    Hyunsook Kim, Sujeong Kim, Dayoung Lee, Dahye Lee, Jiyeon Yoon & Hyukjin Lee

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Kim, H., Kim, S., Lee, D. et al. Oligonucleotide therapeutics and their chemical modification strategies for clinical applications. J. Pharm. Investig. (2024). https://doi.org/10.1007/s40005-024-00669-8

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