FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2318442119> ?p ?o ?g. }

• W2318442119 endingPage "446" @default.
• W2318442119 startingPage "436" @default.
• W2318442119 abstract "Lysosomal storage diseases are an intriguing target for gene therapy approaches, as transduction of a “depot” organ with a transgene encoding a lysosomal enzyme can be followed by secretion, systemic distribution, downstream uptake, and lysosomal targeting of the enzyme into non-transduced tissues. These benefits are of utmost importance when considering gene therapy approaches for glycogen storage disease type-II (GSD-II). GSD-II is a prototypical lysosomal storage disorder caused by lack of intralysosomal acid α-glucosidase (GAA) activity. Lack of GAA can result in a proximal limb myopathy and respiratory and cardiac failure, each due to abnormal glycogen accumulation in the skeletal muscles or cardiac tissues, respectively. After converting the liver into a “depot” organ, we found that intravenous injection of the [E1-,polymerase-]AdGAA vector allowed for hepatic secretion of GAA over an at least 20-fold dosage range. We noted that very low plasma GAA levels (derived from hepatic secretion of GAA) can allow for GAA uptake by muscle tissues (skeletal or cardiac), but significantly higher plasma GAA levels are required before glycogen “cross-correction” can occur in these same tissues. We also demonstrated that liver-specific enhancer/promoters prolonged GAA transgene expression from persistent [E1-,polymerase-] adenovirus based vector genomes for at least 180 days, and significantly diminished the amounts of neutralizing anti-GAA antibodies elicited in this animal model. Finally, we demonstrated that skeletal muscles can also serve as a “depot” organ for GAA secretion, allowing for secretion of GAA and its uptake by noninfected distal tissues, although glycogen reductions in non-injected muscles were not achieved by the latter approach. Lysosomal storage diseases are an intriguing target for gene therapy approaches, as transduction of a “depot” organ with a transgene encoding a lysosomal enzyme can be followed by secretion, systemic distribution, downstream uptake, and lysosomal targeting of the enzyme into non-transduced tissues. These benefits are of utmost importance when considering gene therapy approaches for glycogen storage disease type-II (GSD-II). GSD-II is a prototypical lysosomal storage disorder caused by lack of intralysosomal acid α-glucosidase (GAA) activity. Lack of GAA can result in a proximal limb myopathy and respiratory and cardiac failure, each due to abnormal glycogen accumulation in the skeletal muscles or cardiac tissues, respectively. After converting the liver into a “depot” organ, we found that intravenous injection of the [E1-,polymerase-]AdGAA vector allowed for hepatic secretion of GAA over an at least 20-fold dosage range. We noted that very low plasma GAA levels (derived from hepatic secretion of GAA) can allow for GAA uptake by muscle tissues (skeletal or cardiac), but significantly higher plasma GAA levels are required before glycogen “cross-correction” can occur in these same tissues. We also demonstrated that liver-specific enhancer/promoters prolonged GAA transgene expression from persistent [E1-,polymerase-] adenovirus based vector genomes for at least 180 days, and significantly diminished the amounts of neutralizing anti-GAA antibodies elicited in this animal model. Finally, we demonstrated that skeletal muscles can also serve as a “depot” organ for GAA secretion, allowing for secretion of GAA and its uptake by noninfected distal tissues, although glycogen reductions in non-injected muscles were not achieved by the latter approach." @default.
• W2318442119 created "2016-06-24" @default.
• W2318442119 creator A5000236143 @default.
• W2318442119 creator A5011587117 @default.
• W2318442119 creator A5039631951 @default.
• W2318442119 creator A5043379516 @default.
• W2318442119 creator A5044644907 @default.
• W2318442119 creator A5050148296 @default.
• W2318442119 creator A5083266436 @default.
• W2318442119 creator A5091409527 @default.
• W2318442119 date "2002-04-01" @default.
• W2318442119 modified "2023-10-11" @default.
• W2318442119 title "Efficacy of Gene Therapy for a Prototypical Lysosomal Storage Disease (GSD-II) Is Critically Dependent on Vector Dose, Transgene Promoter, and the Tissues Targeted for Vector Transduction" @default.
• W2318442119 cites W146643018 @default.
• W2318442119 cites W1586130277 @default.
• W2318442119 cites W1971460945 @default.
• W2318442119 cites W1971873142 @default.
• W2318442119 cites W1973754802 @default.
• W2318442119 cites W1980890790 @default.
• W2318442119 cites W2002886319 @default.
• W2318442119 cites W2008260185 @default.
• W2318442119 cites W2009991379 @default.
• W2318442119 cites W2012081613 @default.
• W2318442119 cites W2014585251 @default.
• W2318442119 cites W2019247095 @default.
• W2318442119 cites W2020970293 @default.
• W2318442119 cites W2030487155 @default.
• W2318442119 cites W2046573487 @default.
• W2318442119 cites W2050193680 @default.
• W2318442119 cites W2058350049 @default.
• W2318442119 cites W2072814829 @default.
• W2318442119 cites W2082750310 @default.
• W2318442119 cites W2122377406 @default.
• W2318442119 cites W2127608615 @default.
• W2318442119 cites W2128152284 @default.
• W2318442119 cites W2155898643 @default.
• W2318442119 doi "https://doi.org/10.1006/mthe.2002.0563" @default.
• W2318442119 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/11945071" @default.
• W2318442119 hasPublicationYear "2002" @default.
• W2318442119 type Work @default.
• W2318442119 sameAs 2318442119 @default.
• W2318442119 citedByCount "59" @default.
• W2318442119 countsByYear W23184421192012 @default.
• W2318442119 countsByYear W23184421192013 @default.
• W2318442119 countsByYear W23184421192015 @default.
• W2318442119 countsByYear W23184421192016 @default.
• W2318442119 countsByYear W23184421192017 @default.
• W2318442119 countsByYear W23184421192019 @default.
• W2318442119 countsByYear W23184421192021 @default.
• W2318442119 countsByYear W23184421192022 @default.
• W2318442119 countsByYear W23184421192023 @default.
• W2318442119 crossrefType "journal-article" @default.
• W2318442119 hasAuthorship W2318442119A5000236143 @default.
• W2318442119 hasAuthorship W2318442119A5011587117 @default.
• W2318442119 hasAuthorship W2318442119A5039631951 @default.
• W2318442119 hasAuthorship W2318442119A5043379516 @default.
• W2318442119 hasAuthorship W2318442119A5044644907 @default.
• W2318442119 hasAuthorship W2318442119A5050148296 @default.
• W2318442119 hasAuthorship W2318442119A5083266436 @default.
• W2318442119 hasAuthorship W2318442119A5091409527 @default.
• W2318442119 hasBestOaLocation W23184421191 @default.
• W2318442119 hasConcept C102230213 @default.
• W2318442119 hasConcept C104317684 @default.
• W2318442119 hasConcept C111599444 @default.
• W2318442119 hasConcept C126322002 @default.
• W2318442119 hasConcept C134018914 @default.
• W2318442119 hasConcept C153911025 @default.
• W2318442119 hasConcept C2777499176 @default.
• W2318442119 hasConcept C2779134260 @default.
• W2318442119 hasConcept C2779959927 @default.
• W2318442119 hasConcept C2779969927 @default.
• W2318442119 hasConcept C49039625 @default.
• W2318442119 hasConcept C55493867 @default.
• W2318442119 hasConcept C71924100 @default.
• W2318442119 hasConcept C86803240 @default.
• W2318442119 hasConceptScore W2318442119C102230213 @default.
• W2318442119 hasConceptScore W2318442119C104317684 @default.
• W2318442119 hasConceptScore W2318442119C111599444 @default.
• W2318442119 hasConceptScore W2318442119C126322002 @default.
• W2318442119 hasConceptScore W2318442119C134018914 @default.
• W2318442119 hasConceptScore W2318442119C153911025 @default.
• W2318442119 hasConceptScore W2318442119C2777499176 @default.
• W2318442119 hasConceptScore W2318442119C2779134260 @default.
• W2318442119 hasConceptScore W2318442119C2779959927 @default.
• W2318442119 hasConceptScore W2318442119C2779969927 @default.
• W2318442119 hasConceptScore W2318442119C49039625 @default.
• W2318442119 hasConceptScore W2318442119C55493867 @default.
• W2318442119 hasConceptScore W2318442119C71924100 @default.
• W2318442119 hasConceptScore W2318442119C86803240 @default.
• W2318442119 hasIssue "4" @default.
• W2318442119 hasLocation W23184421191 @default.
• W2318442119 hasLocation W23184421192 @default.
• W2318442119 hasOpenAccess W2318442119 @default.
• W2318442119 hasPrimaryLocation W23184421191 @default.
• W2318442119 hasRelatedWork W1987514107 @default.
• W2318442119 hasRelatedWork W1993212089 @default.
• W2318442119 hasRelatedWork W2149588051 @default.
• W2318442119 hasRelatedWork W2162562000 @default.

• next