ArticleProceedings of the National Academy of Sciences of the United States of America2013
Engineering a lysosomal enzyme with a derivative of receptor-binding domain of apoE enables delivery across the blood-brain barrier.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 156 citations in OpenAlex.
- Review
- Advances in nano-TCM for Alzheimer's disease: lipid-based carriers integrated with innovative delivery strategies.Journal of nanobiotechnology · 2026Review
- Nanotechnology for efficient delivery of TCM active ingredients in treating brain diseases.Materials today. Bio · 2026Review
- Development of a Novel Immunoprecipitation Method for Extracting Monoclonal Antibodies From Brain Tissue and Its Application to Assessing In Vivo Brain Penetration in Mouse via Liquid Chromatography-Mass Spectrometry.Biomedical chromatography : BMC · 2025Article
- From Better Diagnostics to Earlier Treatment: The Rapidly Evolving Alzheimer's Disease Landscape.Medicina (Kaunas, Lithuania) · 2025Review
- Beyond the Walls of Troy: A Scoping Review on Pharmacological Strategies to Enhance Drug Delivery Across the Blood-Brain Barrier and Blood-Tumor Barrier.International journal of molecular sciences · 2025Article
- Exploring the Pharmacological Effects of Bioactive Peptides on Human Nervous Disorders: A Comprehensive Review.CNS & neurological disorders drug targets · 2025Review
- Developing New Peptides and Peptide-Drug Conjugates for Targeting the FGFR2 Receptor-Expressing Tumor Cells and 3D Spheroids.Biomimetics (Basel, Switzerland) · 2024Article
- Receptor Ligand-Free Mesoporous Silica Nanoparticles: A Streamlined Strategy for Targeted Drug Delivery across the Blood-Brain Barrier.ACS nano · 2024Article
- Lentiviral Gene Therapy for Mucopolysaccharidosis II with Tagged Iduronate 2-Sulfatase Prevents Life-Threatening Pathology in Peripheral Tissues But Fails to Correct Cartilage.Human gene therapy · 2024Article
- Unraveling the Genetic Landscape of Neurological Disorders: Insights into Pathogenesis, Techniques for Variant Identification, and Therapeutic Approaches.International journal of molecular sciences · 2024Review
- Tagged IDS causes efficient and engraftment-independent prevention of brain pathology during lentiviral gene therapy for Mucopolysaccharidosis type II.Molecular therapy. Methods & clinical development · 2023Article
- Development of an apolipoprotein E mimetic peptide-lipid conjugate for efficient brain delivery of liposomes.Drug delivery · 2023Article
- Anchoring Microbubbles on Cerebrovascular Endothelium as a New Strategy Enabling Low-Energy Ultrasound-Assisted Delivery of Varisized Agents Across Blood-Brain Barrier.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Peptide-Based Agents for Cancer Treatment: Current Applications and Future Directions.International journal of molecular sciences · 2023Review
- Cell-Penetrating and Targeted Peptides Delivery Systems as Potential Pharmaceutical Carriers for Enhanced Delivery across the Blood-Brain Barrier (BBB).Pharmaceutics · 2023Review
- Targeting the central nervous system in lysosomal storage diseases: Strategies to deliver therapeutics across the blood-brain barrier.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Review
- Article
- Identification of a novel fusion Iduronidase with improved activity in the cardiovascular system.Molecular genetics and metabolism reports · 2022Article
- Peptides as Pharmacological Carriers to the Brain: Promises, Shortcomings and Challenges.Molecular pharmaceutics · 2022Review
15 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
To realize the potential of large molecular weight substances to treat neurological disorders, novel approaches are required to surmount the blood-brain barrier (BBB). We investigated whether fusion of a receptor-binding peptide from apolipoprotein E (apoE) with a potentially therapeutic protein can bind to LDL receptors on the BBB and be transcytosed into the CNS. A lysosomal enzyme, α-L-iduronidase (IDUA), was used for biological and therapeutic evaluation in a mouse model of mucopolysaccharidosis (MPS) type I, one of the most common lysosomal storage disorders with CNS deficits. We identified two fusion candidates, IDUAe1 and IDUAe2, by in vitro screening, that exhibited desirable receptor-mediated binding, endocytosis, and transendothelial transport as well as appropriate lysosomal enzyme trafficking and biological function. Robust peripheral IDUAe1 or IDUAe2 generated by transient hepatic expression led to elevated enzyme levels in capillary-depleted, enzyme-deficient brain tissues and protein delivery into nonendothelium perivascular cells, neurons, and astrocytes within 2 d of treatment. Moreover, 5 mo after long-term delivery of moderate levels of IDUAe1 derived from maturing red blood cells, 2% to 3% of normal brain IDUA activities were obtained in MPS I mice, and IDUAe1 protein was detected in neurons and astrocytes throughout the brain. The therapeutic potential was demonstrated by normalization of brain glycosaminoglycan and β-hexosaminidase in MPS I mice 5 mo after moderate yet sustained delivery of IDUAe1. These findings provide a noninvasive and BBB-targeted procedure for the delivery of large-molecule therapeutic agents to treat neurological lysosomal storage disorders and potentially other diseases that involve the brain.
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Registered trials
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.