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dc.contributor.authorJubair, L
dc.contributor.authorFallaha, S
dc.contributor.authorMcMillan, NAJ
dc.date.accessioned2019-09-27T01:02:36Z
dc.date.available2019-09-27T01:02:36Z
dc.date.issued2019
dc.identifier.issn1525-0016
dc.identifier.doi10.1016/j.ymthe.2019.08.012
dc.identifier.urihttp://hdl.handle.net/10072/387823
dc.description.abstractThe recent advancements in CRISPR/Cas9 engineering have resulted in the development of more targeted and potentially safer gene therapies. The challenge in the cancer setting is knowing the driver oncogenes responsible, and the translation of these therapies is hindered by effective and safe delivery methods to target organs with minimal systemic toxicities, on-target specificity of gene editing, and demonstrated lack of long-term adverse events. Using a model system based on cervical cancer, which is driven by the ongoing expression of the human papillomavirus E6 and E7 proteins, we show that CRISPR/Cas9 delivered systemically in vivo using PEGylated liposomes results in tumor elimination and complete survival in treated animals. We compared treatment and editing efficiency of two Cas9 variants, wild-type (WT) Cas9 and the highly specific FokI-dCas9, and showed that the latter was not effective. We also explored high-fidelity repair but found that repair was inefficient, occurring in 6%–8% of cells, whereas non-homologous end joining (NHEJ) was highly efficient, occurring in ∼80% of the cells. Finally, we explored the post gene-editing events in tumors and showed that cell death is induced by apoptosis. Overall, our work demonstrates that in vivo CRISPR/Cas editing treatment of preexisting tumors is completely effective despite the large payloads.
dc.description.peerreviewedYes
dc.languageEnglish
dc.publisherElsevier
dc.publisher.placeUnited States
dc.relation.ispartofjournalMolecular Therapy
dc.subject.fieldofresearchMedical Microbiology
dc.subject.fieldofresearchClinical Sciences
dc.subject.fieldofresearchBiological Sciences
dc.subject.fieldofresearchTechnology
dc.subject.fieldofresearchMedical and Health Sciences
dc.subject.fieldofresearchcode1108
dc.subject.fieldofresearchcode1103
dc.subject.fieldofresearchcode06
dc.subject.fieldofresearchcode10
dc.subject.fieldofresearchcode11
dc.subject.keywordsCRISPR
dc.subject.keywordsHPV
dc.subject.keywordsgene editing
dc.titleSystemic Delivery of CRISPR/Cas9 Targeting HPV Oncogenes Is Effective at Eliminating Established Tumors
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationJubair, L; Fallaha, S; McMillan, NAJ, Systemic Delivery of CRISPR/Cas9 Targeting HPV Oncogenes Is Effective at Eliminating Established Tumors, Molecular Therapy, 2019
dcterms.dateAccepted2019-08-21
dc.date.updated2019-09-27T00:44:19Z
gro.description.notepublicThis publication has been entered into Griffith Research Online as an Advanced Online Version.
gro.hasfulltextNo Full Text
gro.griffith.authorMcMillan, Nigel
gro.griffith.authorFallaha, Sora
gro.griffith.authorJubair, Luqman K.


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