FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2030144103> ?p ?o ?g. }

• W2030144103 endingPage "S305" @default.
• W2030144103 startingPage "S304" @default.
• W2030144103 abstract "Nonviral gene therapy is being developed for the treatment of Cystic Fibrosis (CF) lung disease. To date, such approaches have been limited by the poor duration of expression observed and a have also resulted in inflammatory responses following delivery of lipid/ plasmid DNA (pDNA) complexes to the lungs of mice and human subjects. This inflammatory response appears to be due in part to the detection by toll-like receptor 9 of CpG motifs present in pDNA. The majority of first generation pDNA vectors used in pre-clinical and clinical studies contained a large number of immune-stimulatory CpG motifs and one approach to reducing inflammation is to reduce or completely remove CpGs from the pDNA. Therefore we have constructed two novel series of pDNA vectors. Second generation pDNA vectors were constructed from elements with a low CpG content (such as the Genzyme ΔCpG plasmid backbone), which reduced the overall number of CpGs by approximately 50%. Third generation plasmids were constructed from elements that contained no CpG motifs (ΔCpG R6K origin, ΔCpG ZeoR, Murine CMV enhancer, human EF1a promoter) to produce zero-CpG plasmids. Versions of these plasmids that expressed luciferase reporter gene were complexed with Genzyme lipid 67 and delivered to mouse lung by nasal instillation (BALB/c, n=10, 80μg pDNA/100μl). At 24-hours post-dosing, bronchoalveolar lavage fluid (BALF) was collected and the level of IL-12, IFN-γ, TNF-α and total cells was determined. Untreated controls mice had very low levels of all four markers (0%). Mice that received CpG-rich first generation plasmid complexes had elevated levels of all four inflammatory markers (100%). Delivery of second generation (CpG-reduced) plasmids to the mouse lung did not significantly reduce levels IL-12 (105%), TNF-α (60%), IFN-γ (86%) or total cells (80%) (Mann-Whitney U P>0.05). However, following delivery of third generation (zero- CpG) plasmid complexes, levels of IL-12 (10%), TNF-α (0%), IFN-γ (4%) and total cells (14%) were indistinguishable from untreated control mice (P<0.01). Furthermore, at 24-hours post- dosing, luciferase activity in the lung was 10-fold higher from third generation plasmids compared with all other treated groups (P<0.001). In addition, expression from the zero-CpG plasmids persisted for at least 60 days post-dosing while the CpG containing plasmids resulted in only transient expression in the mouse lung (<7 days). These studies suggest that partial reduction of CpG content is no sufficient to reduce the inlfammation observed in mouse lung airway gene transfer models. However the lack of an inflammatory response following delivery of zero-CpG plasmids suggests that these vectors represent a significant advance in terms of safety and efficacy of nonviral delivery to the lung. Further studies outlining the development and testing of clinically relevant zero-CpG will also be presented." @default.
• W2030144103 created "2016-06-24" @default.
• W2030144103 creator A5016215295 @default.
• W2030144103 creator A5024231265 @default.
• W2030144103 creator A5028293325 @default.
• W2030144103 creator A5032599226 @default.
• W2030144103 creator A5041655105 @default.
• W2030144103 creator A5051712770 @default.
• W2030144103 creator A5057984337 @default.
• W2030144103 creator A5069237359 @default.
• W2030144103 date "2006-01-01" @default.
• W2030144103 modified "2023-10-18" @default.
• W2030144103 title "786. Development of Zero-CpG Plasmids with Reduced Inflammatory Responses Following Delivery of Lipid/pDNA Complexes to the Mouse Lung" @default.
• W2030144103 doi "https://doi.org/10.1016/j.ymthe.2006.08.873" @default.
• W2030144103 hasPublicationYear "2006" @default.
• W2030144103 type Work @default.
• W2030144103 sameAs 2030144103 @default.
• W2030144103 citedByCount "0" @default.
• W2030144103 crossrefType "journal-article" @default.
• W2030144103 hasAuthorship W2030144103A5016215295 @default.
• W2030144103 hasAuthorship W2030144103A5024231265 @default.
• W2030144103 hasAuthorship W2030144103A5028293325 @default.
• W2030144103 hasAuthorship W2030144103A5032599226 @default.
• W2030144103 hasAuthorship W2030144103A5041655105 @default.
• W2030144103 hasAuthorship W2030144103A5051712770 @default.
• W2030144103 hasAuthorship W2030144103A5057984337 @default.
• W2030144103 hasAuthorship W2030144103A5069237359 @default.
• W2030144103 hasBestOaLocation W20301441031 @default.
• W2030144103 hasConcept C104317684 @default.
• W2030144103 hasConcept C111599444 @default.
• W2030144103 hasConcept C126322002 @default.
• W2030144103 hasConcept C135983454 @default.
• W2030144103 hasConcept C140173407 @default.
• W2030144103 hasConcept C150194340 @default.
• W2030144103 hasConcept C153911025 @default.
• W2030144103 hasConcept C161733203 @default.
• W2030144103 hasConcept C185592680 @default.
• W2030144103 hasConcept C190727270 @default.
• W2030144103 hasConcept C203014093 @default.
• W2030144103 hasConcept C22744801 @default.
• W2030144103 hasConcept C22801619 @default.
• W2030144103 hasConcept C2776914184 @default.
• W2030144103 hasConcept C2777714996 @default.
• W2030144103 hasConcept C2777961210 @default.
• W2030144103 hasConcept C40767141 @default.
• W2030144103 hasConcept C552990157 @default.
• W2030144103 hasConcept C55493867 @default.
• W2030144103 hasConcept C71924100 @default.
• W2030144103 hasConcept C86803240 @default.
• W2030144103 hasConcept C8891405 @default.
• W2030144103 hasConceptScore W2030144103C104317684 @default.
• W2030144103 hasConceptScore W2030144103C111599444 @default.
• W2030144103 hasConceptScore W2030144103C126322002 @default.
• W2030144103 hasConceptScore W2030144103C135983454 @default.
• W2030144103 hasConceptScore W2030144103C140173407 @default.
• W2030144103 hasConceptScore W2030144103C150194340 @default.
• W2030144103 hasConceptScore W2030144103C153911025 @default.
• W2030144103 hasConceptScore W2030144103C161733203 @default.
• W2030144103 hasConceptScore W2030144103C185592680 @default.
• W2030144103 hasConceptScore W2030144103C190727270 @default.
• W2030144103 hasConceptScore W2030144103C203014093 @default.
• W2030144103 hasConceptScore W2030144103C22744801 @default.
• W2030144103 hasConceptScore W2030144103C22801619 @default.
• W2030144103 hasConceptScore W2030144103C2776914184 @default.
• W2030144103 hasConceptScore W2030144103C2777714996 @default.
• W2030144103 hasConceptScore W2030144103C2777961210 @default.
• W2030144103 hasConceptScore W2030144103C40767141 @default.
• W2030144103 hasConceptScore W2030144103C552990157 @default.
• W2030144103 hasConceptScore W2030144103C55493867 @default.
• W2030144103 hasConceptScore W2030144103C71924100 @default.
• W2030144103 hasConceptScore W2030144103C86803240 @default.
• W2030144103 hasConceptScore W2030144103C8891405 @default.
• W2030144103 hasLocation W20301441031 @default.
• W2030144103 hasOpenAccess W2030144103 @default.
• W2030144103 hasPrimaryLocation W20301441031 @default.
• W2030144103 hasRelatedWork W1969661822 @default.
• W2030144103 hasRelatedWork W2056022116 @default.
• W2030144103 hasRelatedWork W2067228485 @default.
• W2030144103 hasRelatedWork W2099781987 @default.
• W2030144103 hasRelatedWork W2149306058 @default.
• W2030144103 hasRelatedWork W2317033267 @default.
• W2030144103 hasRelatedWork W2327204353 @default.
• W2030144103 hasRelatedWork W2327268143 @default.
• W2030144103 hasRelatedWork W2333720988 @default.
• W2030144103 hasRelatedWork W2921766967 @default.
• W2030144103 hasVolume "13" @default.
• W2030144103 isParatext "false" @default.
• W2030144103 isRetracted "false" @default.
• W2030144103 magId "2030144103" @default.
• W2030144103 workType "article" @default.