Rational design of site-specific artificial metallonucleases for therapeutic applications
Rational design of site-specific artificial metallonucleases for therapeutic applications
Artificial metallonucleases (ArMNs) are synthetic nucleases that utilise metals as the catalytic centre for cleaving nucleic acids, with the metal component present in the form of ions, complexes or nanoparticles. ArMNs have been developed as therapeutics for a range of diseases, including genetic disorders, cancer and infectious diseases. Achieving high site-specificity in ArMNs is crucial for their effective application in targeted therapeutic interventions. By employing advanced methodologies, these engineered nucleases can induce targeted modifications in the genome, thereby advancing genetic research, improving disease treatment and fostering biotechnological innovation. This review examines recent advancements over the past 20 years in the design and synthesis of site-specific ArMNs. Illustrated examples are provided to elucidate the underlying principles of their site-specific activity and to highlight their prospective applications. Additionally, strategies for overcoming challenges in enhancing the selectivity of these nucleases are discussed, and anticipated future research directions in this dynamic field are outlined.
Artificial enzymes, Metallonuclease, Site-specific, Therapeutics
Lu, Xi
bb27ecfb-a22e-4fe1-a167-753bd2d48a19
Zhang, Chengchen
abc47c06-4b99-4aed-be72-463f211e9dfa
Lu, Xi
bb27ecfb-a22e-4fe1-a167-753bd2d48a19
Zhang, Chengchen
abc47c06-4b99-4aed-be72-463f211e9dfa
Lu, Xi and Zhang, Chengchen
(2025)
Rational design of site-specific artificial metallonucleases for therapeutic applications.
Microchemical Journal, 213, [113736].
(doi:10.1016/j.microc.2025.113736).
Abstract
Artificial metallonucleases (ArMNs) are synthetic nucleases that utilise metals as the catalytic centre for cleaving nucleic acids, with the metal component present in the form of ions, complexes or nanoparticles. ArMNs have been developed as therapeutics for a range of diseases, including genetic disorders, cancer and infectious diseases. Achieving high site-specificity in ArMNs is crucial for their effective application in targeted therapeutic interventions. By employing advanced methodologies, these engineered nucleases can induce targeted modifications in the genome, thereby advancing genetic research, improving disease treatment and fostering biotechnological innovation. This review examines recent advancements over the past 20 years in the design and synthesis of site-specific ArMNs. Illustrated examples are provided to elucidate the underlying principles of their site-specific activity and to highlight their prospective applications. Additionally, strategies for overcoming challenges in enhancing the selectivity of these nucleases are discussed, and anticipated future research directions in this dynamic field are outlined.
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Accepted/In Press date: 19 April 2025
e-pub ahead of print date: 23 April 2025
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© 2025 The Author(s)
Keywords:
Artificial enzymes, Metallonuclease, Site-specific, Therapeutics
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Local EPrints ID: 502691
URI: http://eprints.soton.ac.uk/id/eprint/502691
ISSN: 0026-265X
PURE UUID: 50d75bc6-2ae3-40e5-857d-b8f63629acae
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Date deposited: 04 Jul 2025 16:43
Last modified: 22 Aug 2025 02:41
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Author:
Xi Lu
Author:
Chengchen Zhang
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