FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2024558818> ?p ?o ?g. }

• W2024558818 endingPage "S81" @default.
• W2024558818 startingPage "S80" @default.
• W2024558818 abstract "The purpose of this project was to evaluate the Sleeping Beauty (SB) transposon for delivery of the human α-L-iduronidase ( IDUA) gene to chromosomes in the livers of IDUA-deficient mice for long- term expression and correction of MPS type I. We chose the hydrodynamics-based DNA injection, which targets mainly the liver. We constructed SB transposon, plasmid-based vectors and injected them into idua-/-mice. Because our goal was in part to determine the efficacy of transposition as a way of providing long-term expression of IDUA protein, control groups of MPS I mice did not get the transposase. Blood samples for plasma isolation were collected 1 day after treatment and once every 2 weeks thereafter. Plasma IDUA activities reached >100-fold of wild type levels on day 1 following treatment, but were essentially gone in all mice 4 weeks following gene delivery. IDUA activity was not detected in the livers of these mice 3 months after plasmid administration. We examined the duration of the transposon-delivered human IDUA DNA maintenance and enzyme activity over 6 months in the liver of wild type (WT) C57Bl/6 mice that express IDUA. As in the MPS I mice, plasma and liver IDUA activity reached supra-normal levels on day 1 and remained at this level for the first week, but still dropped dramatically within 2 weeks and by 4 weeks were indistinguishable from background. Using DNA PCR, we found that the maintenance of the IDUA transgene mirrored the IDUA activity time-line. Even though transposition was confirmed by an excision assay, the PCR product was detectable only for the first two weeks, but not thereafter. It appears that cells that express the IDUA gene are cleared from the liver of treated mice by 4 weeks following injection, which suggests induction of an immune response either to the therapeutic protein or/and the cells that express the therapeutic gene. This hypothesis is supported by our observations that in all cyclophosphamide immune-suppressed MPS I mice, the initial 1-day plasma activity levels dropped more than 100-fold by 2 weeks, but then persisted at 20-500% WT activity in some mice. IDUA levels were stable (up to 5-fold higher than in the WT mice) in SB-transposase-treated MPS I mice whereas without SB, IDUA levels declined to near-background over 3 months. These persistent IDUA activity levels were sufficient to reduce the number and size of pathologic inclusions in the liver seen by toluidine blue staining. Secondary elevation of murine β-glucuronidase, another lysosomal enzyme, was reduced in the liver, spleen and kidney and correlated with degree of reduction of lysosomal pathology in these organs. Thus, with immune suppression, a single dose of the SB transposon system can result in partial to complete biochemical correction of IDUA activity in the livers of treated adult MPS I mice. Perry B. Hackett and R. Scott McIvor have financial interest in Discovery Genomics, Inc." @default.
• W2024558818 created "2016-06-24" @default.
• W2024558818 creator A5003357830 @default.
• W2024558818 creator A5018465635 @default.
• W2024558818 creator A5027934295 @default.
• W2024558818 creator A5032551487 @default.
• W2024558818 creator A5032924224 @default.
• W2024558818 creator A5036401265 @default.
• W2024558818 creator A5037752592 @default.
• W2024558818 creator A5045992163 @default.
• W2024558818 creator A5063827272 @default.
• W2024558818 creator A5069563469 @default.
• W2024558818 date "2006-01-01" @default.
• W2024558818 modified "2023-09-25" @default.
• W2024558818 title "208. Sleeping Beauty Transposon-Mediated Long-Term α-L-iduronidase Expression and Correction of Lysosomal Pathology in the Murine Model of Mucopolysaccharidosis (MPS) Type I" @default.
• W2024558818 doi "https://doi.org/10.1016/j.ymthe.2006.08.233" @default.
• W2024558818 hasPublicationYear "2006" @default.
• W2024558818 type Work @default.
• W2024558818 sameAs 2024558818 @default.
• W2024558818 citedByCount "0" @default.
• W2024558818 crossrefType "journal-article" @default.
• W2024558818 hasAuthorship W2024558818A5003357830 @default.
• W2024558818 hasAuthorship W2024558818A5018465635 @default.
• W2024558818 hasAuthorship W2024558818A5027934295 @default.
• W2024558818 hasAuthorship W2024558818A5032551487 @default.
• W2024558818 hasAuthorship W2024558818A5032924224 @default.
• W2024558818 hasAuthorship W2024558818A5036401265 @default.
• W2024558818 hasAuthorship W2024558818A5037752592 @default.
• W2024558818 hasAuthorship W2024558818A5045992163 @default.
• W2024558818 hasAuthorship W2024558818A5063827272 @default.
• W2024558818 hasAuthorship W2024558818A5069563469 @default.
• W2024558818 hasBestOaLocation W20245588181 @default.
• W2024558818 hasConcept C102230213 @default.
• W2024558818 hasConcept C104317684 @default.
• W2024558818 hasConcept C126322002 @default.
• W2024558818 hasConcept C133288520 @default.
• W2024558818 hasConcept C143065580 @default.
• W2024558818 hasConcept C153911025 @default.
• W2024558818 hasConcept C172510086 @default.
• W2024558818 hasConcept C2779134260 @default.
• W2024558818 hasConcept C2779969927 @default.
• W2024558818 hasConcept C2910509766 @default.
• W2024558818 hasConcept C4918238 @default.
• W2024558818 hasConcept C55493867 @default.
• W2024558818 hasConcept C71924100 @default.
• W2024558818 hasConcept C86803240 @default.
• W2024558818 hasConcept C98274493 @default.
• W2024558818 hasConceptScore W2024558818C102230213 @default.
• W2024558818 hasConceptScore W2024558818C104317684 @default.
• W2024558818 hasConceptScore W2024558818C126322002 @default.
• W2024558818 hasConceptScore W2024558818C133288520 @default.
• W2024558818 hasConceptScore W2024558818C143065580 @default.
• W2024558818 hasConceptScore W2024558818C153911025 @default.
• W2024558818 hasConceptScore W2024558818C172510086 @default.
• W2024558818 hasConceptScore W2024558818C2779134260 @default.
• W2024558818 hasConceptScore W2024558818C2779969927 @default.
• W2024558818 hasConceptScore W2024558818C2910509766 @default.
• W2024558818 hasConceptScore W2024558818C4918238 @default.
• W2024558818 hasConceptScore W2024558818C55493867 @default.
• W2024558818 hasConceptScore W2024558818C71924100 @default.
• W2024558818 hasConceptScore W2024558818C86803240 @default.
• W2024558818 hasConceptScore W2024558818C98274493 @default.
• W2024558818 hasLocation W20245588181 @default.
• W2024558818 hasOpenAccess W2024558818 @default.
• W2024558818 hasPrimaryLocation W20245588181 @default.
• W2024558818 hasRelatedWork W2008114314 @default.
• W2024558818 hasRelatedWork W2025073354 @default.
• W2024558818 hasRelatedWork W2026322742 @default.
• W2024558818 hasRelatedWork W2049246698 @default.
• W2024558818 hasRelatedWork W2056983592 @default.
• W2024558818 hasRelatedWork W2071106547 @default.
• W2024558818 hasRelatedWork W2086105540 @default.
• W2024558818 hasRelatedWork W2151346512 @default.
• W2024558818 hasRelatedWork W2360168182 @default.
• W2024558818 hasRelatedWork W2410953729 @default.
• W2024558818 hasVolume "13" @default.
• W2024558818 isParatext "false" @default.
• W2024558818 isRetracted "false" @default.
• W2024558818 magId "2024558818" @default.
• W2024558818 workType "article" @default.