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References from Delivery architectures for oligonucleotide therapeutics in genetic and rare diseases: GalNAc-based hepatocyte targeting and extrahepatic translation. Local targets link to admitted publications; unresolved targets remain external evidence.
Advances in oligonucleotide drug delivery
10.1038/s41573-020-0075-7 · 2020 · External reference
RNA-targeted therapeutics
10.1016/j.cmet.2018.03.004 · 2018 · External reference
Therapies for rare diseases: therapeutic modalities, progress and challenges ahead
10.1038/s41573-019-0049-9 · 2020 · External reference
Patient-customized oligonucleotide therapy for a rare genetic disease
10.1056/nejmoa1813279 · 2019 · External reference
Unresolved reference
2021 · External reference
Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans
10.1038/35888 · 1998 · External reference
The current state and future directions of RNAi-based therapeutics
10.1038/s41573-019-0017-4 · 2019 · External reference
Patisiran, an RNAi therapeutic, for hereditary transthyretin amyloidosis
10.1056/nejmoa1716153 · 2018 · External reference
The Onpattro story and the clinical translation of nanomedicines containing nucleic acid-based drugs
10.1038/s41565-019-0591-y · 2019 · External reference
Multivalent N-acetylgalactosamine-conjugated siRNA localizes in hepatocytes and elicits robust RNAi-mediated gene silencing
10.1021/ja505986a · 2014 · External reference
Advanced siRNA designs further improve in vivo performance of GalNAc-siRNA conjugates
10.1016/j.ymthe.2017.12.021 · 2018 · External reference
Asialoglycoprotein receptor mediated hepatocyte targeting - strategies and applications
10.1016/j.jconrel.2015.02.022 · 2015 · External reference
The size of endothelial fenestrae in human liver sinusoids: implications for hepatocyte-directed gene transfer
10.1038/gt.2008.60 · 2008 · External reference
Investigating the pharmacodynamic durability of GalNAc-siRNA conjugates
10.1093/nar/gkaa670 · 2020 · External reference
Unresolved reference
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Unresolved reference
2025 · External reference
The approval of Redemplo for familial chylomicronemia syndrome and the many Flavors of GalNAc-oligonucleotides
10.1177/21593337261435980 · 2026 · External reference
Unresolved reference
2025 · External reference
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2025 · External reference
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2025 · External reference
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2025 · External reference
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2025 · External reference
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2025 · External reference
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2026 · External reference
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2025 · External reference
Unresolved reference
2024 · External reference
Unresolved reference
2025 · External reference
The asialoglycoprotein receptor: relationships between structure, function, and expression
10.1152/physrev.1995.75.3.591 · 1995 · External reference
GalNAc-siRNA conjugates: leading the way for delivery of RNAi therapeutics
10.1089/nat.2018.0736 · 2018 · External reference
Preclinical and clinical advances of GalNAc-decorated nucleic acid therapeutics
10.1016/j.omtn.2016.12.003 · 2017 · External reference
Delivery of oligonucleotides to the liver with GalNAc: from research to registered therapeutic drug
10.1016/j.ymthe.2020.06.015 · 2020 · External reference
A divalent siRNA chemical scaffold for potent and sustained modulation of gene expression throughout the central nervous system
10.1038/s41587-019-0205-0 · 2019 · External reference
Expanding RNAi therapeutics to extrahepatic tissues with lipophilic conjugates
10.1038/s41587-022-01334-x · 2022 · External reference
Multiple-dose results from an ongoing phase 1 study of Mivelsiran, an investigational RNA interference therapeutic targeting amyloid-Beta precursor protein for Alzheimer’s disease
10.1002/alz70859_097989 · 2025 · External reference
Unresolved reference
2024 · External reference
Divalent siRNA for prion disease
10.1093/nar/gkag287 · 2026 · External reference
Unresolved reference
2024 · External reference
Unresolved reference
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Unresolved reference
2026 · External reference
Development of antibody-siRNA conjugate targeted to cardiac and skeletal muscles
10.1016/j.jconrel.2016.06.036 · 2016 · External reference
An antibody-oligonucleotide conjugate for myotonic dystrophy type 1
10.1056/nejmoa2407326 · 2026 · External reference
FORCE platform overcomes barriers of oligonucleotide delivery to muscle and corrects myotonic dystrophy features in preclinical models
10.1038/s43856-025-00733-w · 2025 · External reference
Targeted tissue delivery of RNA therapeutics using antibody-oligonucleotide conjugates (AOCs)
10.1093/nar/gkad415 · 2023 · External reference
Local CpG-Stat3 siRNA treatment improves antitumor effects of immune checkpoint inhibitors
10.1016/j.omtn.2024.102357 · 2024 · External reference
Unresolved reference
2021 · External reference
Unresolved reference
2026 · External reference
Unresolved reference
2024 · External reference
Structural basis for 5′-nucleotide base-specific recognition of guide RNA by human AGO2
10.1038/nature09039 · 2010 · External reference
In vivo activity of nuclease-resistant siRNAs
10.1261/rna.5239604 · 2004 · External reference
Characterization of fully 2′-modified oligoribonucleotide hetero- and homoduplex hybridization and nuclease sensitivity
10.1093/nar/23.11.2019 · 1995 · External reference
Fully 2’-modified oligonucleotide duplexes with improved in vitro potency and stability compared to unmodified small interfering RNA
10.1021/jm049167j · 2005 · External reference
Phosphorothioates, essential components of therapeutic oligonucleotides
10.1089/nat.2014.0506 · 2014 · External reference
5′-(E)-Vinylphosphonate: a stable phosphate mimic can improve the RNAi activity of siRNA-GalNAc conjugates
10.1002/cbic.201600130 · 2016 · External reference
5΄-Vinylphosphonate improves tissue accumulation and efficacy of conjugated siRNAs in vivo
10.1093/nar/gkx507 · 2017 · External reference
Selection of GalNAc-conjugated siRNAs with limited off-target-driven rat hepatotoxicity
10.1038/s41467-018-02989-4 · 2018 · External reference
From bench to bedside: improving the clinical safety of GalNAc-siRNA conjugates using seed-pairing destabilization
10.1093/nar/gkac539 · 2022 · External reference
Hepatocyte-specific delivery of siRNAs conjugated to novel non-nucleosidic trivalent N-acetylgalactosamine elicits robust gene silencing in vivo
10.1002/cbic.201500023 · 2015 · External reference
Structural optimization of siRNA conjugates for albumin binding achieves effective MCL1-directed cancer therapy
10.1038/s41467-024-45609-0 · 2024 · External reference
siRNA conjugate with high albumin affinity and degradation resistance for delivery and treatment of arthritis in mice and guinea pigs
10.1038/s41551-025-01376-x · 2025 · External reference
Peptide-oligonucleotide conjugation: chemistry and therapeutic applications
10.3390/cimb46100655 · 2024 · External reference
Unresolved reference
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Lipid conjugates enhance endosomal release of antisense oligonucleotides into cells
10.1089/nat.2019.0794 · 2019 · External reference
Image-based analysis of lipid nanoparticle-mediated siRNA delivery, intracellular trafficking and endosomal escape
10.1038/nbt.2612 · 2013 · External reference
Unresolved reference
2018 · External reference
Insights into the kinetics of siRNA-mediated gene silencing from live-cell and live-animal bioluminescent imaging
10.1093/nar/gkj439 · 2006 · External reference
Phase 3 trial of RNAi therapeutic Givosiran for acute intermittent porphyria
10.1056/nejmoa1913147 · 2020 · External reference
Lumasiran, an RNAi therapeutic for primary hyperoxaluria type 1
10.1056/nejmoa2021712 · 2021 · External reference
Two phase 3 trials of Inclisiran in patients with elevated LDL cholesterol
10.1056/nejmoa1912387 · 2020 · External reference
Vutrisiran in patients with transthyretin amyloidosis with cardiomyopathy
10.1056/nejmoa2409134 · 2025 · External reference
Fitusiran prophylaxis in people with severe haemophilia A or haemophilia B without inhibitors (ATLAS-A/B): a multicentre, open-label, randomised, phase 3 trial
10.1016/s2352-3026(23)00037-6 · 2023 · External reference
Efficacy and safety of fitusiran prophylaxis in people with haemophilia A or haemophilia B with inhibitors (ATLAS-INH): a multicentre, open-label, randomised phase 3 trial
10.1016/s0140-6736(23)00284-2 · 2023 · External reference
Plozasiran for managing persistent chylomicronemia and pancreatitis risk
10.1056/nejmoa2409368 · 2025 · External reference
PHYOX2: a pivotal randomized study of nedosiran in primary hyperoxaluria type 1 or 2
10.1016/j.kint.2022.07.025 · 2023 · External reference
Unresolved reference
2026 · External reference
Unresolved reference
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Targeting the transferrin receptor to transport antisense oligonucleotides across the mammalian blood-brain barrier
10.1126/scitranslmed.adi2245 · 2024 · External reference
Intravenous administration of blood-brain barrier-crossing conjugates facilitate biomacromolecule transport into central nervous system
10.1038/s41587-024-02487-7 · 2025 · External reference
Transferrin receptor (TfR) trafficking determines brain uptake of TfR antibody affinity variants
10.1084/jem.20131660 · 2014 · External reference
The effects of dose, valency, and affinity on TfR-mediated brain delivery in vivo
10.1186/s12987-025-00643-y · 2025 · External reference
Addressing safety liabilities of TfR bispecific antibodies that cross the blood-brain barrier
10.1126/scitranslmed.3005338 · 2013 · External reference
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2024 · External reference
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Development of a DUX4-targeting antibody oligonucleotide conjugate as a therapy for FSHD
10.1093/nar/gkag301 · 2026 · External reference
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Unresolved reference
2026 · External reference
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2025 · External reference
Design of bifunctional RNA-binding compounds that can modulate siRNA hydrophobicity for deep penetration and gene silencing in the retina
10.1016/j.omtn.2025.102751 · 2025 · External reference
Unresolved reference
External reference
RNA-based therapies in inherited retinal diseases
2022 · External reference
Pulmonary siRNA delivery for lung disease: review of recent progress and challenges
10.1016/j.jconrel.2020.11.005 · 2021 · External reference
Dry powder inhalation of siRNA therapeutics: emerging strategies for pulmonary gene silencing
10.1016/j.xphs.2025.104076 · 2026 · External reference
Unresolved reference
2022 · External reference
A first-in-human study of ARO-RAGE, a novel inhaled RNA-interference therapy for asthma
2024 · External reference
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2025 · External reference
Unresolved reference
2020 · External reference
Unresolved reference
2021 · External reference
Megalin and cubilin in proximal tubule protein reabsorption: from experimental models to human disease
10.1016/j.kint.2015.11.007 · 2016 · External reference
Efficient and selective kidney targeting by chemically modified carbohydrate conjugates
10.1016/j.ymthe.2024.10.020 · 2024 · External reference
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2025 · External reference
Unresolved reference
2025 · External reference
Unresolved reference
2025 · External reference
Unresolved reference
2025 · External reference
Unresolved reference
2026 · External reference
A lung-targeted RNAi therapeutics delivery platform compatible with subcutaneous (s.c.) administration mediates pulmonary RAGE silencing in rodents and nonhuman primates
2023 · External reference
Fazirsiran for adults with alpha-1 antitrypsin deficiency liver disease: a phase 2 placebo controlled trial (SEQUOIA)
10.1053/j.gastro.2024.06.028 · 2024 · External reference
Fazirsiran for liver disease associated with alpha(1)-antitrypsin deficiency
10.1056/nejmoa2205416 · 2022 · External reference
Unresolved reference
2023 · External reference
Chemical engineering of therapeutic siRNAs for allele-specific gene silencing in Huntington’s disease models
10.1038/s41467-022-33061-x · 2022 · External reference
Rational design of antisense oligonucleotides targeting single nucleotide polymorphisms for potent and allele selective suppression of mutant Huntingtin in the CNS
10.1093/nar/gkt725 · 2013 · External reference
Huntington’s disease clinical trials update: March 2025
10.1177/18796397251337000 · 2025 · External reference
Tominersen in adults with manifest Huntington’s disease
10.1056/nejmc2300400 · 2023 · External reference
Trial of antisense oligonucleotide tofersen for SOD1 ALS
10.1056/nejmoa2204705 · 2022 · External reference
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2024 · External reference
Unresolved reference
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RNA interference with zilebesiran for mild to moderate hypertension: the KARDIA-1 randomized clinical trial
10.1001/jama.2024.0728 · 2024 · External reference
Add-on treatment with zilebesiran for inadequately controlled hypertension: the KARDIA-2 randomized clinical trial
10.1001/jama.2025.6681 · 2025 · External reference
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Small interfering RNA to reduce lipoprotein(a) in cardiovascular disease
10.1056/nejmoa2211023 · 2022 · External reference
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2026 · External reference
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1999 · External reference
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Unresolved reference
2023 · External reference
Visualizing lipid-formulated siRNA release from endosomes and target gene knockdown
10.1038/nbt.3298 · 2015 · External reference
Delivery of RNA therapeutics: the great endosomal escape!
10.1089/nat.2022.0004 · 2022 · External reference
Imaging small molecule-induced endosomal escape of siRNA
10.1038/s41467-020-15300-1 · 2020 · External reference
Engineered ionizable lipid siRNA conjugates enhance endosomal escape but induce toxicity in vivo
10.1016/j.jconrel.2022.07.041 · 2022 · External reference
Unresolved reference
2023 · External reference
Eplontersen for treating hereditary transthyretin-related amyloidosis
2024 · External reference
Unresolved reference
2021 · External reference
Unresolved reference
2025 · External reference