FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2800100380> ?p ?o ?g. }

• W2800100380 endingPage "4844" @default.
• W2800100380 startingPage "4833" @default.
• W2800100380 abstract "Familial dysautonomia (FD) is a rare inherited neurodegenerative disorder caused by a point mutation in the IKBKAP gene that results in defective splicing of its pre-mRNA. The mutation weakens the 5′ splice site of exon 20, causing this exon to be skipped, thereby introducing a premature termination codon. Though detailed FD pathogenesis mechanisms are not yet clear, correcting the splicing defect in the relevant tissue(s), thus restoring normal expression levels of the full-length IKAP protein, could be therapeutic. Splice-switching antisense oligonucleotides (ASOs) can be effective targeted therapeutics for neurodegenerative diseases, such as nusinersen (Spinraza), an approved drug for spinal muscular atrophy. Using a two-step screen with ASOs targeting IKBKAP exon 20 or the adjoining intronic regions, we identified a lead ASO that fully restored exon 20 splicing in FD patient fibroblasts. We also characterized the corresponding cis-acting regulatory sequences that control exon 20 splicing. When administered into a transgenic FD mouse model, the lead ASO promoted expression of full-length human IKBKAP mRNA and IKAP protein levels in several tissues tested, including the central nervous system. These findings provide insights into the mechanisms of IKBKAP exon 20 recognition, and pre-clinical proof of concept for an ASO-based targeted therapy for FD." @default.
• W2800100380 created "2018-05-17" @default.
• W2800100380 creator A5004106287 @default.
• W2800100380 creator A5017886173 @default.
• W2800100380 creator A5029149817 @default.
• W2800100380 creator A5041605141 @default.
• W2800100380 creator A5057673768 @default.
• W2800100380 creator A5067326228 @default.
• W2800100380 creator A5082344505 @default.
• W2800100380 creator A5083296071 @default.
• W2800100380 date "2018-04-17" @default.
• W2800100380 modified "2023-10-14" @default.
• W2800100380 title "Antisense oligonucleotides correct the familial dysautonomia splicing defect in IKBKAP transgenic mice" @default.
• W2800100380 cites W1871517579 @default.
• W2800100380 cites W1967340903 @default.
• W2800100380 cites W1979117468 @default.
• W2800100380 cites W1993689991 @default.
• W2800100380 cites W2000725203 @default.
• W2800100380 cites W2021406306 @default.
• W2800100380 cites W2025722577 @default.
• W2800100380 cites W2037367916 @default.
• W2800100380 cites W2040531711 @default.
• W2800100380 cites W2060725188 @default.
• W2800100380 cites W2063777609 @default.
• W2800100380 cites W2080990756 @default.
• W2800100380 cites W2092908962 @default.
• W2800100380 cites W2093095283 @default.
• W2800100380 cites W2106579945 @default.
• W2800100380 cites W2113631912 @default.
• W2800100380 cites W2115222513 @default.
• W2800100380 cites W2119887502 @default.
• W2800100380 cites W2121006987 @default.
• W2800100380 cites W2126789530 @default.
• W2800100380 cites W2134441015 @default.
• W2800100380 cites W2136930242 @default.
• W2800100380 cites W2142450777 @default.
• W2800100380 cites W2149564698 @default.
• W2800100380 cites W2155560336 @default.
• W2800100380 cites W2157912726 @default.
• W2800100380 cites W2166556264 @default.
• W2800100380 cites W2167256464 @default.
• W2800100380 cites W2194209300 @default.
• W2800100380 cites W2304775097 @default.
• W2800100380 cites W2343116876 @default.
• W2800100380 cites W2344897797 @default.
• W2800100380 cites W2420632962 @default.
• W2800100380 cites W2482730706 @default.
• W2800100380 cites W2555626897 @default.
• W2800100380 cites W2560202024 @default.
• W2800100380 cites W2565737694 @default.
• W2800100380 cites W2604270443 @default.
• W2800100380 cites W2623178876 @default.
• W2800100380 cites W2725911567 @default.
• W2800100380 cites W2752779752 @default.
• W2800100380 cites W4250943273 @default.
• W2800100380 doi "https://doi.org/10.1093/nar/gky249" @default.
• W2800100380 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6007753" @default.
• W2800100380 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29672717" @default.
• W2800100380 hasPublicationYear "2018" @default.
• W2800100380 type Work @default.
• W2800100380 sameAs 2800100380 @default.
• W2800100380 citedByCount "45" @default.
• W2800100380 countsByYear W28001003802018 @default.
• W2800100380 countsByYear W28001003802019 @default.
• W2800100380 countsByYear W28001003802020 @default.
• W2800100380 countsByYear W28001003802021 @default.
• W2800100380 countsByYear W28001003802022 @default.
• W2800100380 countsByYear W28001003802023 @default.
• W2800100380 crossrefType "journal-article" @default.
• W2800100380 hasAuthorship W2800100380A5004106287 @default.
• W2800100380 hasAuthorship W2800100380A5017886173 @default.
• W2800100380 hasAuthorship W2800100380A5029149817 @default.
• W2800100380 hasAuthorship W2800100380A5041605141 @default.
• W2800100380 hasAuthorship W2800100380A5057673768 @default.
• W2800100380 hasAuthorship W2800100380A5067326228 @default.
• W2800100380 hasAuthorship W2800100380A5082344505 @default.
• W2800100380 hasAuthorship W2800100380A5083296071 @default.
• W2800100380 hasBestOaLocation W28001003801 @default.
• W2800100380 hasConcept C102230213 @default.
• W2800100380 hasConcept C104317684 @default.
• W2800100380 hasConcept C153911025 @default.
• W2800100380 hasConcept C166342232 @default.
• W2800100380 hasConcept C176944494 @default.
• W2800100380 hasConcept C194583182 @default.
• W2800100380 hasConcept C2778558090 @default.
• W2800100380 hasConcept C2779696190 @default.
• W2800100380 hasConcept C36823959 @default.
• W2800100380 hasConcept C501734568 @default.
• W2800100380 hasConcept C54355233 @default.
• W2800100380 hasConcept C54458228 @default.
• W2800100380 hasConcept C67705224 @default.
• W2800100380 hasConcept C86803240 @default.
• W2800100380 hasConcept C95444343 @default.
• W2800100380 hasConceptScore W2800100380C102230213 @default.
• W2800100380 hasConceptScore W2800100380C104317684 @default.
• W2800100380 hasConceptScore W2800100380C153911025 @default.
• W2800100380 hasConceptScore W2800100380C166342232 @default.
• W2800100380 hasConceptScore W2800100380C176944494 @default.

• next