| http://purl.uniprot.org/citations/24821812 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/24821812 | http://www.w3.org/2000/01/rdf-schema#comment | "The acute hepatic porphyrias are inherited disorders of heme biosynthesis characterized by life-threatening acute neurovisceral attacks. Factors that induce the expression of hepatic 5-aminolevulinic acid synthase 1 (ALAS1) result in the accumulation of the neurotoxic porphyrin precursors 5-aminolevulinic acid (ALA) and porphobilinogen (PBG), which recent studies indicate are primarily responsible for the acute attacks. Current treatment of these attacks involves i.v. administration of hemin, but a faster-acting, more effective, and safer therapy is needed. Here, we describe preclinical studies of liver-directed small interfering RNAs (siRNAs) targeting Alas1 (Alas1-siRNAs) in a mouse model of acute intermittent porphyria, the most common acute hepatic porphyria. A single i.v. dose of Alas1-siRNA prevented the phenobarbital-induced biochemical acute attacks for approximately 2 wk. Injection of Alas1-siRNA during an induced acute attack significantly decreased plasma ALA and PBG levels within 8 h, more rapidly and effectively than a single hemin infusion. Alas1-siRNA was well tolerated and a therapeutic dose did not cause hepatic heme deficiency. These studies provide proof-of-concept for the clinical development of RNA interference therapy for the prevention and treatment of the acute attacks of the acute hepatic porphyrias."xsd:string |
| http://purl.uniprot.org/citations/24821812 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.1406228111"xsd:string |
| http://purl.uniprot.org/citations/24821812 | http://purl.uniprot.org/core/author | "Chen B."xsd:string |
| http://purl.uniprot.org/citations/24821812 | http://purl.uniprot.org/core/author | "Gan L."xsd:string |
| http://purl.uniprot.org/citations/24821812 | http://purl.uniprot.org/core/author | "New M.I."xsd:string |
| http://purl.uniprot.org/citations/24821812 | http://purl.uniprot.org/core/author | "Yu C."xsd:string |
| http://purl.uniprot.org/citations/24821812 | http://purl.uniprot.org/core/author | "Yasuda M."xsd:string |
| http://purl.uniprot.org/citations/24821812 | http://purl.uniprot.org/core/author | "Phillips J.D."xsd:string |
| http://purl.uniprot.org/citations/24821812 | http://purl.uniprot.org/core/author | "Fitzgerald K."xsd:string |
| http://purl.uniprot.org/citations/24821812 | http://purl.uniprot.org/core/author | "Desnick R.J."xsd:string |
| http://purl.uniprot.org/citations/24821812 | http://purl.uniprot.org/core/author | "Querbes W."xsd:string |
| http://purl.uniprot.org/citations/24821812 | http://purl.uniprot.org/core/author | "Kadirvel S."xsd:string |
| http://purl.uniprot.org/citations/24821812 | http://purl.uniprot.org/core/author | "Liebow A."xsd:string |
| http://purl.uniprot.org/citations/24821812 | http://purl.uniprot.org/core/date | "2014"xsd:gYear |
| http://purl.uniprot.org/citations/24821812 | http://purl.uniprot.org/core/name | "Proc Natl Acad Sci U S A"xsd:string |
| http://purl.uniprot.org/citations/24821812 | http://purl.uniprot.org/core/pages | "7777-7782"xsd:string |
| http://purl.uniprot.org/citations/24821812 | http://purl.uniprot.org/core/title | "RNAi-mediated silencing of hepatic Alas1 effectively prevents and treats the induced acute attacks in acute intermittent porphyria mice."xsd:string |
| http://purl.uniprot.org/citations/24821812 | http://purl.uniprot.org/core/volume | "111"xsd:string |
| http://purl.uniprot.org/citations/24821812 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/24821812 |
| http://purl.uniprot.org/citations/24821812 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/24821812 |
| http://purl.uniprot.org/uniprot/Q8VC19#attribution-138E39C70EBC57850634B554A2862F4E | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/24821812 |
| http://purl.uniprot.org/uniprot/#_A0A0R4J0X2-mappedCitation-24821812 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24821812 |
| http://purl.uniprot.org/uniprot/#_A0A1L1STE9-mappedCitation-24821812 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24821812 |
| http://purl.uniprot.org/uniprot/#_A0A1L1SUZ0-mappedCitation-24821812 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24821812 |