Matches in SemOpenAlex for { <https://semopenalex.org/work/W4247352392> ?p ?o ?g. }
Showing items 1 to 81 of
81
with 100 items per page.
- W4247352392 abstract "Abstract Background Mutated KRAS promotes the activation of mitogen-activated protein kinase (MAPK) pathway and the progression of colorectal cancer (CRC) cells. Aberrant activation of phosphatidylinositol 3‑kinase (PI3K) pathway strongly attenuates the efficacy of MAPK suppression in KRAS-mutated CRC cells. The development of a novel strategy targeting dual-pathway is therefore highly essential for the therapy of KRAS-mutated CRC cells. Methods In this study, a quadruple-depleting system for KRAS, MEK1, PIK3CA, and mammalian target of rapamycin (MTOR) genes based on Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/SaCas9 was developed. Serotype 5 of adenovirus (ADV5) was used as packaging virus for systemic delivery of the CRISPR system. To enhance infection efficiency and specificity of ADV5 to CRC cells and reduce its non-specific tissue tropism, two engineered proteins, an adaptor and a protector were synthesized and formed an ADV-protein complex (APC) when delivered the quadruple-editing system intravenously in vivo . Results The quadruple-editing significantly inhibited MAPK and PI3K pathways in CRC cells with oncogenic mutations of KRAS and PIK3CA or with KRAS mutation and compensated PI3K activation. Compared with MEK and PI3K/MTOR inhibitors, the quadruple-editing induced more significant survival inhibition on primary CRC cells with oncogenic mutations of KRAS and PIK3CA. The adaptor protein which specifically targeting epithelial cell adhesion molecule (EpCAM) could dramatically enhance infection efficiency of ADV5 to CRC cells. and the protector protein could significantly reduce the off-targeting tropisms in a variety of organs. Moreover, the quadruple-editing intravenously delivered by APC significantly blocked dual-pathway and tumor growth, without influencing normal tissues in cell- and patient-derived xenograft models of KRAS-mutated CRC cells. Conclusions APC-delivered quadruple-editing of MAPK and PI3K pathways effectively and specifically blocked the progression of KRAS-mutated CRC cells." @default.
- W4247352392 created "2022-05-12" @default.
- W4247352392 creator A5003593721 @default.
- W4247352392 creator A5010383816 @default.
- W4247352392 creator A5019278466 @default.
- W4247352392 creator A5029409137 @default.
- W4247352392 creator A5030840389 @default.
- W4247352392 creator A5043904245 @default.
- W4247352392 creator A5050424155 @default.
- W4247352392 creator A5052883326 @default.
- W4247352392 creator A5057328522 @default.
- W4247352392 creator A5058380236 @default.
- W4247352392 creator A5059807822 @default.
- W4247352392 creator A5070368039 @default.
- W4247352392 creator A5082755814 @default.
- W4247352392 creator A5090685571 @default.
- W4247352392 date "2021-02-24" @default.
- W4247352392 modified "2023-09-25" @default.
- W4247352392 title "Quadruple-editing of MAPK and PI3K pathways effectively blocks the progression of KRAS-mutated colorectal cancer cells" @default.
- W4247352392 doi "https://doi.org/10.21203/rs.3.rs-230629/v1" @default.
- W4247352392 hasPublicationYear "2021" @default.
- W4247352392 type Work @default.
- W4247352392 citedByCount "0" @default.
- W4247352392 crossrefType "posted-content" @default.
- W4247352392 hasAuthorship W4247352392A5003593721 @default.
- W4247352392 hasAuthorship W4247352392A5010383816 @default.
- W4247352392 hasAuthorship W4247352392A5019278466 @default.
- W4247352392 hasAuthorship W4247352392A5029409137 @default.
- W4247352392 hasAuthorship W4247352392A5030840389 @default.
- W4247352392 hasAuthorship W4247352392A5043904245 @default.
- W4247352392 hasAuthorship W4247352392A5050424155 @default.
- W4247352392 hasAuthorship W4247352392A5052883326 @default.
- W4247352392 hasAuthorship W4247352392A5057328522 @default.
- W4247352392 hasAuthorship W4247352392A5058380236 @default.
- W4247352392 hasAuthorship W4247352392A5059807822 @default.
- W4247352392 hasAuthorship W4247352392A5070368039 @default.
- W4247352392 hasAuthorship W4247352392A5082755814 @default.
- W4247352392 hasAuthorship W4247352392A5090685571 @default.
- W4247352392 hasBestOaLocation W42473523921 @default.
- W4247352392 hasConcept C104317684 @default.
- W4247352392 hasConcept C121608353 @default.
- W4247352392 hasConcept C184235292 @default.
- W4247352392 hasConcept C2781187634 @default.
- W4247352392 hasConcept C502942594 @default.
- W4247352392 hasConcept C526805850 @default.
- W4247352392 hasConcept C54355233 @default.
- W4247352392 hasConcept C57074206 @default.
- W4247352392 hasConcept C62478195 @default.
- W4247352392 hasConcept C86554907 @default.
- W4247352392 hasConcept C86803240 @default.
- W4247352392 hasConcept C95444343 @default.
- W4247352392 hasConcept C98108389 @default.
- W4247352392 hasConceptScore W4247352392C104317684 @default.
- W4247352392 hasConceptScore W4247352392C121608353 @default.
- W4247352392 hasConceptScore W4247352392C184235292 @default.
- W4247352392 hasConceptScore W4247352392C2781187634 @default.
- W4247352392 hasConceptScore W4247352392C502942594 @default.
- W4247352392 hasConceptScore W4247352392C526805850 @default.
- W4247352392 hasConceptScore W4247352392C54355233 @default.
- W4247352392 hasConceptScore W4247352392C57074206 @default.
- W4247352392 hasConceptScore W4247352392C62478195 @default.
- W4247352392 hasConceptScore W4247352392C86554907 @default.
- W4247352392 hasConceptScore W4247352392C86803240 @default.
- W4247352392 hasConceptScore W4247352392C95444343 @default.
- W4247352392 hasConceptScore W4247352392C98108389 @default.
- W4247352392 hasLocation W42473523921 @default.
- W4247352392 hasOpenAccess W4247352392 @default.
- W4247352392 hasPrimaryLocation W42473523921 @default.
- W4247352392 hasRelatedWork W2004726042 @default.
- W4247352392 hasRelatedWork W2106300588 @default.
- W4247352392 hasRelatedWork W2216439242 @default.
- W4247352392 hasRelatedWork W2261929084 @default.
- W4247352392 hasRelatedWork W2339535453 @default.
- W4247352392 hasRelatedWork W2384817912 @default.
- W4247352392 hasRelatedWork W2744901703 @default.
- W4247352392 hasRelatedWork W3035328115 @default.
- W4247352392 hasRelatedWork W3134645471 @default.
- W4247352392 hasRelatedWork W4310603292 @default.
- W4247352392 isParatext "false" @default.
- W4247352392 isRetracted "false" @default.
- W4247352392 workType "article" @default.