ArticleProceedings of the National Academy of Sciences of the United States of America2014
RNAi-mediated silencing of hepatic Alas1 effectively prevents and treats the induced acute attacks in acute intermittent porphyria mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 124 citations in OpenAlex.
- The Role of Cytochrome P450 Holoenzyme Metabolism in the Origin of Neuropathologies.International journal of molecular sciences · 2026Review
- A gasdermin-based life-death evolution system for reprogramming protease specificity.Nature chemical biology · 2026Article
- Animal Models of Porphyria with Hepatic Involvement.Seminars in liver disease · 2025Review
- How multispecific molecules are transforming pharmacotherapy.Nature reviews. Drug discovery · 2025Review
- Small Interfering RNA Therapy Targeting the Long Noncoding RNA SMILR for Therapeutic Intervention in Coronary Artery Bypass Graft Failure.JACC. Basic to translational science · 2025Article
- Advancing Therapeutic Strategies with Polymeric Drug Conjugates for Nucleic Acid Delivery and Treatment.International journal of nanomedicine · 2025Review
- Noncanonical role of ALAS1 as a heme-independent inhibitor of small RNA-mediated silencing.Science (New York, N.Y.) · 2024Article
- Givosiran: a targeted treatment for acute intermittent porphyria.Hematology. American Society of Hematology. Education Program · 2024Review
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- Unleashing the potential of catalytic RNAs to combat mis-spliced transcripts.Frontiers in bioengineering and biotechnology · 2023Review
- Therapeutic siRNA: State-of-the-Art and Future Perspectives.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2022Review
- Novel Gene-Correction-Based Therapeutic Modalities for Monogenic Liver Disorders.Bioengineering (Basel, Switzerland) · 2022Review
- Therapy Follows Diagnosis: Old and New Approaches for the Treatment of Acute Porphyrias, What We Know and What We Should Know.Diagnostics (Basel, Switzerland) · 2022Review
- Therapeutic RNA-silencing oligonucleotides in metabolic diseases.Nature reviews. Drug discovery · 2022Review
- Cutting-Edge Therapies and Novel Strategies for Acute Intermittent Porphyria: Step-by-Step towards the Solution.Biomedicines · 2022Review
- An RNAi therapeutic targeting hepatic DGAT2 in a genetically obese mouse model of nonalcoholic steatohepatitis.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Recent Advances in RNA Therapy and Its Carriers to Treat the Single-Gene Neurological Disorders.Biomedicines · 2022Review
- Spotlight on Givosiran as a Treatment Option for Adults with Acute Hepatic Porphyria: Design, Development, and Place in Therapy.Drug design, development and therapy · 2022Review
5 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.