@article{9f9d4f80dc4446f4a5f68df9bb9d017f,
title = "Therapeutic gene silencing of CKAP5 leads to lethality in genetically unstable cancer cells",
abstract = "The potential of microtubule-associated protein targets for cancer therapeutics remains largely unexplored due to the lack of target-specific agents. Here, we explored the therapeutic potential of targeting cytoskeleton-associated protein 5 (CKAP5), an important microtubule-associated protein, with CKAP5-targeting siRNAs encapsulated in lipid nanoparticles (LNPs). Our screening of 20 solid cancer cell lines demonstrated selective vulnerability of genetically unstable cancer cell lines in response to CKAP5 silencing. We identified a highly responsive chemo-resistant ovarian cancer cell line, in which CKAP5 silencing led to significant loss in EB1 dynamics during mitosis. Last, we demonstrated the therapeutic potential in an in vivo ovarian cancer model, showing 80% survival rate of siCKAP5 LNPs-treated animals. Together, our results highlight the importance of CKAP5 as a therapeutic target for genetically unstable ovarian cancer and warrants further investigation into its mechanistic aspects.",
keywords = "Humans, Animals, Female, Gene Silencing, Microtubule-Associated Proteins/metabolism, RNA, Small Interfering/genetics, Microtubules/metabolism, Ovarian Neoplasms/genetics, Nanoparticles",
author = "Sushmita Chatterjee and Naidu, {Gonna Somu} and Inbal Hazan-Halevy and Hanna Grobe and Assaf Ezra and Preeti Sharma and Meir Goldsmith and Srinivas Ramishetti and David Sprinzak and Ronen Zaidel-Bar and Dan Peer",
note = "Funding Information: Acknowledgments:W eacknowledgethemicroscopyandFA CS facilityofT el A viv University medical ZABAM unit. S.C. received postdoctoral fellowship from PBC/V A T A T . W e thank E. Kon andU.Eliaforhelpingineditingthemanuscript.Funding:Thisworkwasfundedinpartbythe ShmunisFamilyTrust,bytheRivkinFoundation,andbytheIsraelScienceFoundationgrant numbers1178/16and3150/19awardedtoD.P .Authorcontributions:Conceptualization:D.P . andS.C.Methodology:S.C.,I.H.-H.,G.S.N.,S.R.,A.E.,H.G.,P .S., andM.G.Investigation:D.P ., S.C., I.H.-H.,S.R.,P .S., andM.G.Visualization:D.P ., S.C.,R.Z.-B.,andD.S.Supervision:D.P ., D.S.,andR.Z.-B. Writing–original draft: S.C. Writing–review and editing: D.P ., I.H.-H., and R.Z.-B. Competing interests:D.P .declaresthefollowingcompetingfinancialinterest(s):D.P .receiveslicensingfees (topatentsonwhichhewasaninventor)from,investedin,consults(oronscientificadvisory boardsorboardsofdirectors)for,lectured(andreceivedafee),orconductssponsoredresearch atT AU forthefollowingentities:ARTBiosciences,BioNtechSE,EarliInc.,KernalBiologics,Merck, NewphaseLtd.,NeoVacLtd.,RiboXTherapeutics,Roche,SirTLabsCorporation,andT eva PharmaceuticalsInc.Allotherauthorsdeclarethattheyhavenocompetinginterests.Dataand materialsavailability:Alldataneededtoevaluatetheconclusionsinthepaperarepresentin thepaperand/ortheSupplementaryMaterials. Publisher Copyright: Copyright {\textcopyright} 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).",
year = "2023",
month = apr,
day = "5",
doi = "10.1126/sciadv.ade4800",
language = "English (US)",
volume = "9",
pages = "eade4800",
journal = "Science advances",
issn = "2375-2548",
publisher = "American Association for the Advancement of Science",
number = "14",
}