- Title
- A novel approach to nonsurgical sterilization; application of menadione-modified gonocyte-targeting M13 bacteriophage for germ cell ablation in utero
- Creator
- Fraser, Barbara A.; Miller, Kasey; Trigg, Natalie A.; Smith, Nathan D.; Western, Patrick S.; Nixon, Brett; Aitken, Robert J.
- Relation
- ARC.DP150103231 http://purl.org/au-research/grants/arc/DP150103231
- Relation
- Pharmacology Research & Perspectives Vol. 8, Issue 5, no. e00654
- Publisher Link
- http://dx.doi.org/10.1002/prp2.654
- Publisher
- John Wiley & Sons
- Resource Type
- journal article
- Date
- 2020
- Description
- There remains a compelling need for the development of nonsurgical sterilizing agents to expand the fertility management options for both domestic and feral animal species. We hypothesize that an efficacious sterilization approach would be to selectively ablate nonrenewable cell types that are essential for reproduction, such as the undifferentiated gonocytes within the embryonic gonad. Here, we report a novel strategy to achieve this goal centered on the use of a chemically modified M13 bacteriophage to effect the targeted delivery of menadione, a redox-cycling naphthoquinone, to mouse gonocytes. Panning of the M13 random peptide ‘phage display library proved effective in the isolation of gonocyte-specific targeting clones. One such clone was modified via N-succinimidyl-S-acetylthioacetate (SATA) linkage to the N-terminus of the major PVIII capsid protein. Subsequent deacetylation of the SATA was undertaken to expose a thiol group capable of reacting with menadione through Michael addition. This chemical modification was confirmed using UV spectrophotometry. In proof-of-concept experiments we applied the modified ‘phage to primary cultures of fetal germ cells and induced, an approximately, 60% reduction in the viability of the target cell population. These studies pave the way for in vivo application of chemically modified M13 bacteriophage in order to achieve the selective ablation of nonrenewable cell types in the reproductive system, thereby providing a novel nonsurgical approach the regulation of fertility in target species.
- Subject
- (MeSH): 'phage display; bacteriophage; contraceptive; gonocytes; menadione; ROS
- Identifier
- http://hdl.handle.net/1959.13/1425791
- Identifier
- uon:38313
- Identifier
- ISSN:2052-1707
- Rights
- © 2020 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd . This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
- Language
- eng
- Full Text
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