{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T15:39:59Z","timestamp":1775144399904,"version":"3.50.1"},"reference-count":196,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2020,8,10]],"date-time":"2020-08-10T00:00:00Z","timestamp":1597017600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Portuguese Society for Metabolic Disorders (Sociedade Portuguesa de Doen\u00e7as Metab\u00f3licas, SPDM","award":["Bolsa SPDM de apoio \u00e0 investiga\u00e7\u00e3o Dr. Aguinaldo Cabral 2018; 2019DGH1629\/SPDM2018I&D"],"award-info":[{"award-number":["Bolsa SPDM de apoio \u00e0 investiga\u00e7\u00e3o Dr. Aguinaldo Cabral 2018; 2019DGH1629\/SPDM2018I&D"]}]},{"DOI":"10.13039\/100013918","name":"Sanfilippo Children's Foundation","doi-asserted-by":"publisher","award":["Incubator Grant 2019; 2019DGH1656\/SCF2019I&D"],"award-info":[{"award-number":["Incubator Grant 2019; 2019DGH1656\/SCF2019I&D"]}],"id":[{"id":"10.13039\/100013918","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>More than two thirds of Lysosomal Storage Diseases (LSDs) present central nervous system involvement. Nevertheless, only one of the currently approved therapies has an impact on neuropathology. Therefore, alternative approaches are under development, either addressing the underlying enzymatic defect or its downstream consequences. Also under study is the possibility to block substrate accumulation upstream, by promoting a decrease of its synthesis. This concept is known as substrate reduction therapy and may be triggered by several molecules, such as small interfering RNAs (siRNAs). siRNAs promote RNA interference, a naturally occurring sequence-specific post-transcriptional gene-silencing mechanism, and may target virtually any gene of interest, inhibiting its expression. Still, naked siRNAs have limited cellular uptake, low biological stability, and unfavorable pharmacokinetics. Thus, their translation into clinics requires proper delivery methods. One promising platform is a special class of liposomes called stable nucleic acid lipid particles (SNALPs), which are characterized by high cargo encapsulation efficiency and may be engineered to promote targeted delivery to specific receptors. Here, we review the concept of SNALPs, presenting a series of examples on their efficacy as siRNA nanodelivery systems. By doing so, we hope to unveil the therapeutic potential of these nanosystems for targeted brain delivery of siRNAs in LSDs.<\/jats:p>","DOI":"10.3390\/ijms21165732","type":"journal-article","created":{"date-parts":[[2020,8,10]],"date-time":"2020-08-10T09:04:16Z","timestamp":1597050256000},"page":"5732","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Lysosomal Storage Disease-Associated Neuropathy: Targeting Stable Nucleic Acid Lipid Particle (SNALP)-Formulated siRNAs to the Brain as a Therapeutic Approach"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2222-3622","authenticated-orcid":false,"given":"Maria Francisca","family":"Coutinho","sequence":"first","affiliation":[{"name":"Research and Development Unit, Department of Human Genetics, National Institute of Health Doutor Ricardo Jorge (INSA I.P), Rua Alexandre Herculano, 321, 4000-055 Porto, Portugal"},{"name":"Center for the Study of Animal Science, CECA-ICETA, University of Porto, Pra\u00e7a Gomes Teixeira, Apartado 55142, 4051-401 Porto, Portugal"}]},{"given":"Juliana In\u00eas","family":"Santos","sequence":"additional","affiliation":[{"name":"Research and Development Unit, Department of Human Genetics, National Institute of Health Doutor Ricardo Jorge (INSA I.P), Rua Alexandre Herculano, 321, 4000-055 Porto, Portugal"},{"name":"Biology Department, Faculty of Sciences, University of Porto, Rua do Campo Alegre, 4169-007 Porto, Portugal"}]},{"given":"Liliana","family":"S. Mendon\u00e7a","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"CIBB\u2014Center for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-504 Coimbra, Portugal"}]},{"given":"Liliana","family":"Matos","sequence":"additional","affiliation":[{"name":"Research and Development Unit, Department of Human Genetics, National Institute of Health Doutor Ricardo Jorge (INSA I.P), Rua Alexandre Herculano, 321, 4000-055 Porto, Portugal"},{"name":"Center for the Study of Animal Science, CECA-ICETA, University of Porto, Pra\u00e7a Gomes Teixeira, Apartado 55142, 4051-401 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0583-1028","authenticated-orcid":false,"given":"Maria Jo\u00e3o","family":"Prata","sequence":"additional","affiliation":[{"name":"Biology Department, Faculty of Sciences, University of Porto, Rua do Campo Alegre, 4169-007 Porto, Portugal"},{"name":"i3S\u2014Institute of Research and Innovation in Health\/IPATIMUP\u2014Institute of Molecular Pathology and Immunology of the University of Porto, Rua Alfredo Allen, 208 4200-135 Porto, Portugal"}]},{"given":"Am\u00e1lia","family":"S. Jurado","sequence":"additional","affiliation":[{"name":"University of Coimbra, CNC\u2014Center for Neuroscience and Cell Biology, Department of Life Sciences, Cal\u00e7ada Martim de Freitas, 3000-456 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1844-5027","authenticated-orcid":false,"given":"Maria C.","family":"Pedroso de Lima","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8881-9197","authenticated-orcid":false,"given":"Sandra","family":"Alves","sequence":"additional","affiliation":[{"name":"Research and Development Unit, Department of Human Genetics, National Institute of Health Doutor Ricardo Jorge (INSA I.P), Rua Alexandre Herculano, 321, 4000-055 Porto, Portugal"},{"name":"Center for the Study of Animal Science, CECA-ICETA, University of Porto, Pra\u00e7a Gomes Teixeira, Apartado 55142, 4051-401 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1038\/35888","article-title":"Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans","volume":"391","author":"Fire","year":"1998","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1126\/science.286.5441.950","article-title":"A species of small antisense RNA in posttranscriptional gene silencing in plants","volume":"286","author":"Hamilton","year":"1999","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1038\/35078107","article-title":"Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells","volume":"411","author":"Elbashir","year":"2001","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1101\/gad.862301","article-title":"RNA interference is mediated by 21- and 22-nucleotide RNAs","volume":"15","author":"Elbashir","year":"2001","journal-title":"Genes Dev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"215","DOI":"10.2144\/05392RV01","article-title":"Mammalian RNAi: A practical guide","volume":"39","author":"Sandy","year":"2005","journal-title":"Biotechniques"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/978-3-030-19966-1_7","article-title":"RNA Therapeutics: How Far Have We Gone?","volume":"1157","author":"Coutinho","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.gene.2013.12.019","article-title":"Therapeutic potentials of gene silencing by RNA interference: Principles, challenges, and new strategies","volume":"538","author":"Deng","year":"2014","journal-title":"Gene"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.pneurobio.2016.10.002","article-title":"Emerging therapies for neuropathic lysosomal storage disorders","volume":"152","author":"Kelly","year":"2017","journal-title":"Prog. Neurobiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.paed.2010.08.012","article-title":"Lysosomal disorders","volume":"21","author":"Wraith","year":"2011","journal-title":"Paediatr. Child Health"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1517\/14712598.2011.582036","article-title":"Gene therapy for lysosomal storage disorders","volume":"11","author":"Gritti","year":"2011","journal-title":"Expert Opin. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1038\/s41572-018-0037-0","article-title":"Author Correction: Lysosomal storage diseases","volume":"4","author":"Platt","year":"2018","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Mehta, A., and Winchester, B. (2012). The lysosomal system: Physiology and pathology. Lysosomal Storage Disorders\u2014A Practial Guide, Wiley-Blackwell. [1st ed.].","DOI":"10.1002\/9781118514672"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1172\/JCI5826","article-title":"Molecular basis of variant pseudo-hurler polydystrophy (mucolipidosis IIIC)","volume":"105","author":"Bao","year":"2000","journal-title":"J. Clin. Investig."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1038\/nm1305","article-title":"Mucolipidosis II is caused by mutations in GNPTA encoding the alpha\/beta GlcNAc-1-phosphotransferase","volume":"11","author":"Tiede","year":"2005","journal-title":"Nat. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1203\/00006450-200001000-00007","article-title":"Ocular nonnephropathic cystinosis: Clinical, biochemical, and molecular correlations","volume":"47","author":"Anikster","year":"2000","journal-title":"Pediatr. Res."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Metha, A., and Winchester, B. (2012). Laboratory diagnosis of Lysosomal Storage Diseases. Lysosomal Storage Disorders\u2014A Practial Guide, Wiley-Blackwell. [1st ed.].","DOI":"10.1002\/9781118514672"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"719","DOI":"10.4161\/auto.19469","article-title":"Autophagy in lysosomal storage disorders","volume":"8","author":"Lieberman","year":"2012","journal-title":"Autophagy"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/s10545-008-1040-5","article-title":"Pathogenic cascades in lysosomal disease-Why so complex?","volume":"32","author":"Walkley","year":"2009","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1126\/science.1174447","article-title":"A gene network regulating lysosomal biogenesis and function","volume":"325","author":"Sardiello","year":"2009","journal-title":"Science"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Mehta, A.B., and Winchester, B. (2012). Current Treatments. Lysosomal Storage Disorders\u2014A Practial Guide, Wiley-Blackwell. [1st ed.].","DOI":"10.1002\/9781118514672"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/1758-907X-2-3","article-title":"Off-target effects dominate a large-scale RNAi screen for modulators of the TGF-\u03b2 pathway and reveal microRNA regulation of TGFBR2","volume":"2","author":"Schultz","year":"2011","journal-title":"Silence"},{"key":"ref_22","unstructured":"Mehta, A.B., and Winchester, B. (2012). Central Nervous System Aspects, Neurodegeneration and the Blood-Brain Barrier. Lysosomal Storage Disorders\u2014A Practical Guide, Wiley-Blackwell. [1st ed.]."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Metha, A., and Winchester, B. (2012). Clinical Aspects and Clinical Diagnosis. Lysosomal Storage Disorders\u2014A Practial Guide, Wiley-Blackwell. [1st ed.].","DOI":"10.1002\/9781118514672.ch3"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.spen.2008.05.005","article-title":"Current strategies in the management of lysosomal storage diseases","volume":"15","author":"Heese","year":"2008","journal-title":"Semin. Pediatr. Neurol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1542\/peds.2011-0078","article-title":"Natural history of infantile G(M2) gangliosidosis","volume":"128","author":"Bley","year":"2011","journal-title":"Pediatrics"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"471325","DOI":"10.1155\/2012\/471325","article-title":"Glycosaminoglycan storage disorders: A review","volume":"2012","author":"Coutinho","year":"2012","journal-title":"Biochem. Res. Int."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/BF00313321","article-title":"Sanfilippo B syndrome (MPS III B): Case report with analysis of CSF mucopolysaccharides and conjunctival biopsy","volume":"225","author":"Federico","year":"1981","journal-title":"J. Neurol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1007\/s10545-005-0069-y","article-title":"Heparan sulfate levels in mucopolysaccharidoses and mucolipidoses","volume":"28","author":"Tomatsu","year":"2005","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/s10545-005-5673-3","article-title":"Keratan sulphate levels in mucopolysaccharidoses and mucolipidoses","volume":"28","author":"Tomatsu","year":"2005","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2538","DOI":"10.1002\/ajmg.a.32294","article-title":"Intrathecal enzyme replacement therapy in a patient with mucopolysaccharidosis type I and symptomatic spinal cord compression","volume":"146A","author":"Vieira","year":"2008","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1093\/rheumatology\/ker394","article-title":"Overview of the mucopolysaccharidoses","volume":"50","author":"Muenzer","year":"2011","journal-title":"Rheumatology (Oxford)"},{"key":"ref_32","unstructured":"Scriver, C.R. (2001). The Mucopolysaccharidoses. The Metabolic Basis of Inherited Disease, McGraw-Hill."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1542\/peds.2008-0416","article-title":"Mucopolysaccharidosis I: Management and treatment guidelines","volume":"123","author":"Muenzer","year":"2009","journal-title":"Pediatrics"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1542\/peds.2007-1350","article-title":"Recognition and diagnosis of mucopolysaccharidosis II (Hunter syndrome)","volume":"121","author":"Martin","year":"2008","journal-title":"Pediatrics"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Heon-Roberts, R., Nguyen, A.L.A., and Pshezhetsky, A.V. (2020). Molecular Bases of Neurodegeneration and Cognitive Decline, the Major Burden of Sanfilippo Disease. J. Clin. Med., 9.","DOI":"10.3390\/jcm9020344"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Paciotti, S., Albi, E., Parnetti, L., and Beccari, T. (2020). Lysosomal Ceramide Metabolism Disorders: Implications in Parkinson\u2019s Disease. J. Clin. Med., 9.","DOI":"10.3390\/jcm9020594"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.cbpa.2019.10.006","article-title":"Glycosphingolipids and lysosomal storage disorders as illustrated by gaucher disease","volume":"53","author":"Aerts","year":"2019","journal-title":"Curr. Opin. Chem. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Mehta, A.B., and Winchester, B. (2012). Gaucher Disease. Lysosomal Storage Disorders\u2014A Practical Guide, Wiley-Blackwell. [1st ed.].","DOI":"10.1002\/9781118514672"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3191","DOI":"10.1093\/brain\/awx285","article-title":"Excessive burden of lysosomal storage disorder gene variants in Parkinson\u2019s disease","volume":"140","author":"Robak","year":"2017","journal-title":"Brain"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Blumenreich, S., Barav, O.B., Jenkins, B.J., and Futerman, A.H. (2020). Lysosomal Storage Disorders Shed Light on Lysosomal Dysfunction in Parkinson\u2019s Disease. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21144966"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"476","DOI":"10.21037\/atm.2018.11.39","article-title":"Lysosomal storage disease overview","volume":"6","author":"Sun","year":"2018","journal-title":"Ann. Transl. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/S1474-4422(18)30368-5","article-title":"Clinical challenges and future therapeutic approaches for neuronal ceroid lipofuscinosis","volume":"18","author":"Mole","year":"2019","journal-title":"Lancet. Neurol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Mehta, A.B., and Winchester, B. (2012). Neuronal Ceroid Lipofuscinoses. Lysosomal Storage Disorders\u2014A Practical Guide, Wiley-Blackwell. [1st ed.].","DOI":"10.1002\/9781118514672"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Garbade, S.F., Zielonka, M., Mechler, K., K\u00f6lker, S., Hoffmann, G.F., Staufner, C., Mengel, E., and Ries, M. (2020). FDA orphan drug designations for lysosomal storage disorders\u2014A cross-sectional analysis. PLoS ONE, 15.","DOI":"10.1101\/2020.01.05.20016568"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1542\/peds.2006-2156","article-title":"Enzyme replacement therapy in patients who have mucopolysaccharidosis I and are younger than 5 years: Results of a multinational study of recombinant human alpha-L-iduronidase (laronidase)","volume":"120","author":"Wraith","year":"2007","journal-title":"Pediatrics"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1542\/peds.2007-3847","article-title":"Long-term efficacy and safety of laronidase in the treatment of mucopolysaccharidosis I","volume":"123","author":"Clarke","year":"2009","journal-title":"Pediatrics"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1097\/01.gim.0000232477.37660.fb","article-title":"A phase II\/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome)","volume":"8","author":"Muenzer","year":"2006","journal-title":"Genet. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.jpeds.2005.12.014","article-title":"Enzyme replacement therapy for mucopolysaccharidosis VI: A phase 3, randomized, double-blind, placebo-controlled, multinational study of recombinant human N-acetylgalactosamine 4-sulfatase (recombinant human arylsulfatase B or rhASB) and follow-on, open-label extension study","volume":"148","author":"Harmatz","year":"2006","journal-title":"J. Pediatr."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1097\/GIM.0b013e318206786f","article-title":"Idursulfase treatment of Hunter syndrome in children younger than 6 years: Results from the Hunter Outcome Survey","volume":"13","author":"Muenzer","year":"2011","journal-title":"Genet. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1097\/GIM.0b013e3181fea459","article-title":"Long-term, open-labeled extension study of idursulfase in the treatment of Hunter syndrome","volume":"13","author":"Muenzer","year":"2011","journal-title":"Genet. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.ymgme.2011.02.018","article-title":"Incidence and timing of infusion-related reactions in patients with mucopolysaccharidosis type II (Hunter syndrome) on idursulfase therapy in the real-world setting: A perspective from the Hunter Outcome Survey (HOS)","volume":"103","author":"Burton","year":"2011","journal-title":"Mol. Genet. Metab."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Meng, Y., Sohar, I., Wang, L., Sleat, D.E., and Lobel, P. (2012). Systemic administration of tripeptidyl peptidase I in a mouse model of late infantile neuronal ceroid lipofuscinosis: Effect of glycan modification. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0040509"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/S0142-9612(00)00193-9","article-title":"Peptide and protein PEGylation: A review of problems and solutions","volume":"22","author":"Veronese","year":"2001","journal-title":"Biomaterials"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1038\/nrd1033","article-title":"Effect of pegylation on pharmaceuticals","volume":"2","author":"Harris","year":"2003","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2928","DOI":"10.1021\/mp500258p","article-title":"Insulin receptor antibody-sulfamidase fusion protein penetrates the primate blood-brain barrier and reduces glycosoaminoglycans in Sanfilippo type A cells","volume":"11","author":"Boado","year":"2014","journal-title":"Mol. Pharm."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2999","DOI":"10.1073\/pnas.1222742110","article-title":"Engineering a lysosomal enzyme with a derivative of receptor-binding domain of apoE enables delivery across the blood-brain barrier","volume":"110","author":"Wang","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"de Los Reyes, E., Lehwald, L., Augustine, E.F., Berry-Kravis, E., Butler, K., Cormier, N., Demarest, S., Lu, S., Madden, J., and Olaya, J. (2020). Intracerebroventricular Cerliponase Alfa for Neuronal Ceroid Lipofuscinosis Type 2 Disease: Clinical Practice Considerations From US Clinics. Pediatr. Neurol.","DOI":"10.1016\/j.pediatrneurol.2020.04.018"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2760","DOI":"10.1093\/hmg\/ddr175","article-title":"Intracerebroventricular enzyme infusion corrects central nervous system pathology and dysfunction in a mouse model of metachromatic leukodystrophy","volume":"20","author":"Stroobants","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1002\/ana.22262","article-title":"Highly phosphomannosylated enzyme replacement therapy for GM2 gangliosidosis","volume":"69","author":"Tsuji","year":"2011","journal-title":"Ann. Neurol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"14870","DOI":"10.1073\/pnas.1416660111","article-title":"Delivery of an enzyme-IGFII fusion protein to the mouse brain is therapeutic for mucopolysaccharidosis type IIIB","volume":"111","author":"Kan","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"S59","DOI":"10.1016\/j.ymgme.2013.12.128","article-title":"Intracerebroventricular enzyme replacement therapy with glycosylation-independent lysosomal targeted NAGLU leads to widespread enzymatic activity, reduction of lysosomal storage and of secondary defects in brain of mice with Sanfilippo syndrome type B","volume":"111","author":"Kan","year":"2014","journal-title":"Mol. Genet. Metab."},{"key":"ref_62","first-page":"213","article-title":"Changing Times for CLN2 Disease: The Era of Enzyme Replacement Therapy","volume":"16","author":"Specchio","year":"2020","journal-title":"Clin. Risk Manag."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.molmed.2006.06.001","article-title":"Stop-codon read-through for patients affected by a lysosomal storage disorder","volume":"12","author":"Brooks","year":"2006","journal-title":"Trends Mol. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1002\/jnr.23790","article-title":"Suppression of galactocerebrosidase premature termination codon and rescue of galactocerebrosidase activity in twitcher cells","volume":"94","author":"Luddi","year":"2016","journal-title":"J. Neurosci. Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/j.bbadis.2017.12.014","article-title":"Amlexanox provides a potential therapy for nonsense mutations in the lysosomal storage disorder Aspartylglucosaminuria","volume":"1864","author":"Banning","year":"2018","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2712","DOI":"10.1016\/j.bbadis.2015.09.011","article-title":"Functional analysis of splicing mutations in the IDS gene and the use of antisense oligonucleotides to exploit an alternative therapy for MPS II","volume":"1852","author":"Matos","year":"2015","journal-title":"Biochim. Biophys. Acta."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Matos, L., Duarte, A.J., Ribeiro, D., Chaves, J., Amaral, O., and Alves, S. (2018). Correction of a Splicing Mutation Affecting an Unverricht-Lundborg Disease Patient by Antisense Therapy. Genes, 9.","DOI":"10.3390\/genes9090455"},{"key":"ref_68","first-page":"775","article-title":"Development of an Antisense Oligonucleotide-Mediated Exon Skipping Therapeutic Strategy for Mucolipidosis II: Validation at RNA Level","volume":"31","author":"Matos","year":"2020","journal-title":"Hum. Gene"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Crivaro, A.N., Mucci, J.M., Bondar, C.M., Ormazabal, M.E., Ceci, R., Simonaro, C., and Rozenfeld, P.A. (2019). Efficacy of pentosan polysulfate in in vitro models of lysosomal storage disorders: Fabry and Gaucher Disease. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0217780"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"746","DOI":"10.2174\/1566524015666150921105658","article-title":"Combined Therapies for Lysosomal Storage Diseases","volume":"15","author":"Malinowska","year":"2015","journal-title":"Curr. Mol. Med."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Coutinho, M.F., Santos, J.I., Matos, L., and Alves, S. (2016). Genetic Substrate Reduction Therapy: A Promising Approach for Lysosomal Storage Disorders. Diseases, 4.","DOI":"10.3390\/diseases4040033"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2983","DOI":"10.1007\/s11095-011-0604-5","article-title":"RNA interference and cancer therapy","volume":"28","author":"Wang","year":"2011","journal-title":"Pharm. Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1038\/nrd2742","article-title":"Knocking down barriers: Advances in siRNA delivery","volume":"8","author":"Whitehead","year":"2009","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.addr.2007.03.005","article-title":"RNAi therapeutics: Principles, prospects and challenges","volume":"59","author":"Aagaard","year":"2007","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"John, B., Enright, A.J., Aravin, A., Tuschl, T., Sander, C., and Marks, D.S. (2004). Human MicroRNA targets. PloS Biol., 2.","DOI":"10.1371\/journal.pbio.0020363"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1124\/dmd.106.009555","article-title":"Intravenously administered short interfering RNA accumulates in the kidney and selectively suppresses gene function in renal proximal tubules","volume":"34","author":"Boerman","year":"2006","journal-title":"Drug Metab. Dispos."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1021\/mp800051m","article-title":"Factors affecting the clearance and biodistribution of polymeric nanoparticles","volume":"5","author":"Alexis","year":"2008","journal-title":"Mol. Pharm."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1016\/j.addr.2010.03.008","article-title":"Engineering RNA for targeted siRNA delivery and medical application","volume":"62","author":"Guo","year":"2010","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1038\/nri2448","article-title":"Exploring the full spectrum of macrophage activation","volume":"8","author":"Mosser","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.jconrel.2015.05.035","article-title":"Targeting glucose uptake of glioma cells by siRNA delivery with polymer nanoparticle","volume":"213","author":"Xu","year":"2015","journal-title":"J. Control. Release"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1038\/nm1191","article-title":"Sequence-specific potent induction of IFN-alpha by short interfering RNA in plasmacytoid dendritic cells through TLR7","volume":"11","author":"Hornung","year":"2005","journal-title":"Nat. Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/nmeth854","article-title":"3\u2032 UTR seed matches, but not overall identity, are associated with RNAi off-targets","volume":"3","author":"Birmingham","year":"2006","journal-title":"Nat. Methods"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1261\/rna.25706","article-title":"Widespread siRNA \u201coff-target\u201d transcript silencing mediated by seed region sequence complementarity","volume":"12","author":"Jackson","year":"2006","journal-title":"RNA"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nrd3010","article-title":"Recognizing and avoiding siRNA off-target effects for target identification and therapeutic application","volume":"9","author":"Jackson","year":"2010","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1016\/j.actbio.2010.11.033","article-title":"The mechanism of selective transfection mediated by pentablock copolymers; part II: Nuclear entry and endosomal escape","volume":"7","author":"Zhang","year":"2011","journal-title":"Acta. Biomater."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.arr.2015.03.001","article-title":"siRNA as a tool to improve the treatment of brain diseases: Mechanism, targets and delivery","volume":"21","author":"Gomes","year":"2015","journal-title":"Ageing Res. Rev."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.bcmd.2006.07.002","article-title":"RNAi-mediated inhibition of the glucosylceramide synthase (GCS) gene: A preliminary study towards a therapeutic strategy for Gaucher disease and other glycosphingolipid storage diseases","volume":"37","author":"Grinberg","year":"2006","journal-title":"Blood Cells Mol. Dis."},{"key":"ref_88","first-page":"82","article-title":"Management of Gaucher disease: Enzyme replacement therapy","volume":"12","author":"Zimran","year":"2014","journal-title":"Pediatr. Endocrinol. Rev."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1016\/S0140-6736(00)02161-9","article-title":"Novel oral treatment of Gaucher\u2019s disease with N-butyldeoxynojirimycin (OGT 918) to decrease substrate biosynthesis","volume":"355","author":"Cox","year":"2000","journal-title":"Lancet"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1136\/jmedgenet-2012-101070","article-title":"Miglustat as a therapeutic agent: Prospects and caveats","volume":"49","author":"Venier","year":"2012","journal-title":"J. Med. Genet."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"171","DOI":"10.4103\/jrpp.JRPP_18_24","article-title":"The Clinical Efficacy of Imiglucerase versus Eliglustat in Patients with Gaucher\u2019s Disease Type 1: A Systematic Review","volume":"7","author":"Nabizadeh","year":"2018","journal-title":"J. Res. Pharm. Pr."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1042\/BST0380695","article-title":"Genistein: A natural isoflavone with a potential for treatment of genetic diseases","volume":"38","author":"Wegrzyn","year":"2010","journal-title":"Biochem. Soc. Trans."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.ymgme.2012.04.002","article-title":"Rhodamine B and 2-acetamido-1,3,6-tri-O-acetyl-4-deoxy-4-fluoro-D-glucopyranose (F-GlcNAc) inhibit chondroitin\/dermatan and keratan sulphate synthesis by different mechanisms in bovine chondrocytes","volume":"106","author":"Marais","year":"2012","journal-title":"Mol. Genet. Metab."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1038\/ejhg.2009.144","article-title":"Impairment of glycosaminoglycan synthesis in mucopolysaccharidosis type IIIA cells by using siRNA: A potential therapeutic approach for Sanfilippo disease","volume":"18","author":"Dziedzic","year":"2010","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"293","DOI":"10.18388\/abp.2012_2154","article-title":"Simultaneous siRNA-mediated silencing of pairs of genes coding for enzymes involved in glycosaminoglycan synthesis","volume":"59","author":"Dziedzic","year":"2012","journal-title":"Acta Biochim. Pol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1038\/ejhg.2009.143","article-title":"Gene silencing of EXTL2 and EXTL3 as a substrate deprivation therapy for heparan sulphate storing mucopolysaccharidoses","volume":"18","author":"Kaidonis","year":"2010","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"697","DOI":"10.18388\/abp.2012_2113","article-title":"Comparison of siRNA-mediated silencing of glycosaminoglycan synthesis genes and enzyme replacement therapy for mucopolysaccharidosis in cell culture studies","volume":"59","author":"Chmielarz","year":"2012","journal-title":"Acta. Biochim. Pol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"13654","DOI":"10.1038\/srep13654","article-title":"EXTL2 and EXTL3 inhibition with siRNAs as a promising substrate reduction therapy for Sanfilippo C syndrome","volume":"5","author":"Canals","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"101616","DOI":"10.1016\/j.scr.2019.101616","article-title":"Generation of two compound heterozygous HGSNAT-mutated lines from healthy induced pluripotent stem cells using CRISPR\/Cas9 to model Sanfilippo C syndrome","volume":"41","author":"Cozar","year":"2019","journal-title":"Stem Cell Res."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Benet\u00f3, N., Cozar, M., Castilla-Vallmanya, L., Zetterdahl, O.G., Sacultanu, M., Segur-Bailach, E., Garc\u00eda-Morant, M., Ribes, A., Ahlenius, H., and Grinberg, D. (2020). Neuronal and Astrocytic Differentiation from Sanfilippo C Syndrome iPSCs for Disease Modeling and Drug Development. J. Clin. Med., 9.","DOI":"10.3390\/jcm9030644"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/nrd.2017.214","article-title":"Emptying the stores: Lysosomal diseases and therapeutic strategies","volume":"17","author":"Platt","year":"2018","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/1758-907X-1-14","article-title":"A status report on RNAi therapeutics","volume":"1","author":"Vaishnaw","year":"2010","journal-title":"Silence"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1021\/ar300048p","article-title":"Lipid-based nanoparticles for siRNA delivery in cancer therapy: Paradigms and challenges","volume":"45","author":"Fonseca","year":"2012","journal-title":"ACC Chem. Res."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Tatiparti, K., Sau, S., Kashaw, S.K., and Iyer, A.K. (2017). siRNA Delivery Strategies: A Comprehensive Review of Recent Developments. Nanomaterials, 7.","DOI":"10.3390\/nano7040077"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1038\/nbt1402","article-title":"A combinatorial library of lipid-like materials for delivery of RNAi therapeutics","volume":"26","author":"Akinc","year":"2008","journal-title":"Nat. Biotechnol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1038\/nbt.1602","article-title":"Rational design of cationic lipids for siRNA delivery","volume":"28","author":"Semple","year":"2010","journal-title":"Nat. Biotechnol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1369\/0022155411410885","article-title":"Biodistribution of small interfering RNA at the organ and cellular levels after lipid nanoparticle-mediated delivery","volume":"59","author":"Shi","year":"2011","journal-title":"J. Histochem. Cytochem."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1038\/nrg3978","article-title":"Knocking down disease: A progress report on siRNA therapeutics","volume":"16","author":"Wittrup","year":"2015","journal-title":"Nat. Rev. Genet."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1038\/mt.2010.85","article-title":"Targeted delivery of RNAi therapeutics with endogenous and exogenous ligand-based mechanisms","volume":"18","author":"Akinc","year":"2010","journal-title":"Mol. Ther."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1111\/cbdd.12052","article-title":"siRNA delivery: From lipids to cell-penetrating peptides and their mimics","volume":"80","author":"Gooding","year":"2012","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1038\/nrendo.2011.57","article-title":"RNAi-based therapeutic strategies for metabolic disease","volume":"7","author":"Czech","year":"2011","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1056\/NEJMoa1208760","article-title":"Safety and efficacy of RNAi therapy for transthyretin amyloidosis","volume":"369","author":"Coelho","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1186\/s13023-015-0326-6","article-title":"Efficacy and safety of patisiran for familial amyloidotic polyneuropathy: A phase II multi-dose study","volume":"10","author":"Suhr","year":"2015","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1089\/oli.2009.0180","article-title":"siRNA and innate immunity","volume":"19","author":"Robbins","year":"2009","journal-title":"Oligonucleotides"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1016\/j.cmet.2018.03.004","article-title":"RNA-Targeted Therapeutics","volume":"27","author":"Crooke","year":"2018","journal-title":"Cell Metab."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/S1359-6446(05)03668-8","article-title":"Harnessing in vivo siRNA delivery for drug discovery and therapeutic development","volume":"11","author":"Xie","year":"2006","journal-title":"Drug Discov. Today"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.jconrel.2005.05.018","article-title":"Transporting silence: Design of carriers for siRNA to angiogenic endothelium","volume":"109","author":"Schiffelers","year":"2005","journal-title":"J. Control. Release"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.jconrel.2006.08.017","article-title":"Accelerated blood clearance of PEGylated liposomes upon repeated injections: Effect of doxorubicin-encapsulation and high-dose first injection","volume":"115","author":"Ishida","year":"2006","journal-title":"J. Control. Release"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.jconrel.2006.01.005","article-title":"Injection of PEGylated liposomes in rats elicits PEG-specific IgM, which is responsible for rapid elimination of a second dose of PEGylated liposomes","volume":"112","author":"Ishida","year":"2006","journal-title":"J. Control. Release"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0005-2736(01)00399-6","article-title":"Characterization of the inhibitory effect of PEG-lipid conjugates on the intracellular delivery of plasmid and antisense DNA mediated by cationic lipid liposomes","volume":"1558","author":"Song","year":"2002","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1078\/0171-9335-00363","article-title":"PEGylation significantly affects cellular uptake and intracellular trafficking of non-viral gene delivery particles","volume":"83","author":"Mishra","year":"2004","journal-title":"Eur. J. Cell Biol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1002\/hep.20702","article-title":"Activity of stabilized short interfering RNA in a mouse model of hepatitis B virus replication","volume":"41","author":"Morrissey","year":"2005","journal-title":"Hepatology"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1038\/nbt1122","article-title":"Potent and persistent in vivo anti-HBV activity of chemically modified siRNAs","volume":"23","author":"Morrissey","year":"2005","journal-title":"Nat. Biotechnol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/nature04688","article-title":"RNAi-mediated gene silencing in non-human primates","volume":"441","author":"Zimmermann","year":"2006","journal-title":"Nature"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1056\/NEJMoa040583","article-title":"Intensive versus moderate lipid lowering with statins after acute coronary syndromes","volume":"350","author":"Cannon","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1038\/nature03121","article-title":"Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs","volume":"432","author":"Soutschek","year":"2004","journal-title":"Nature"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1086\/504267","article-title":"Postexposure protection of guinea pigs against a lethal ebola virus challenge is conferred by RNA interference","volume":"193","author":"Geisbert","year":"2006","journal-title":"J. Infect. Dis."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1896","DOI":"10.1016\/S0140-6736(10)60357-1","article-title":"Postexposure protection of non-human primates against a lethal Ebola virus challenge with RNA interference: A proof-of-concept study","volume":"375","author":"Geisbert","year":"2010","journal-title":"Lancet"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1172\/JCI37515","article-title":"Confirming the RNAi-mediated mechanism of action of siRNA-based cancer therapeutics in mice","volume":"119","author":"Judge","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.ccr.2005.06.003","article-title":"Induction of apoptosis by an inhibitor of the mitotic kinesin KSP requires both activation of the spindle assembly checkpoint and mitotic slippage","volume":"8","author":"Tao","year":"2005","journal-title":"Cancer Cell"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"5789","DOI":"10.1073\/pnas.1031523100","article-title":"Polo-like kinase (Plk)1 depletion induces apoptosis in cancer cells","volume":"100","author":"Liu","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.cub.2006.12.037","article-title":"BI 2536, a potent and selective inhibitor of polo-like kinase 1, inhibits tumor growth in vivo","volume":"17","author":"Steegmaier","year":"2007","journal-title":"Curr. Biol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"S27.004","DOI":"10.1212\/WNL.88.16_supplement.S27.004","article-title":"Phase 2 Open-Label Extension (OLE) Study of Patisiran, an Investigational RNA interference (RNAi) Therapeutic for the Treatment of Hereditary ATTR Amyloidosis with Polyneuropathy (S27.004)","volume":"88","author":"Adams","year":"2017","journal-title":"Neurology"},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Adams, D., Suhr, O.B., Dyck, P.J., Litchy, W.J., Leahy, R.G., Chen, J., Gollob, J., and Coelho, T. (2017). Trial design and rationale for APOLLO, a Phase 3, placebo-controlled study of patisiran in patients with hereditary ATTR amyloidosis with polyneuropathy. BMC Neurol., 17.","DOI":"10.1186\/s12883-017-0948-5"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1007\/s40265-018-0983-6","article-title":"Patisiran: First Global Approval","volume":"78","author":"Hoy","year":"2018","journal-title":"Drugs"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1016\/j.drudis.2006.07.005","article-title":"Exploiting the enhanced permeability and retention effect for tumor targeting","volume":"11","author":"Iyer","year":"2006","journal-title":"Drug Discov. Today"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.addr.2010.04.009","article-title":"The EPR effect: Unique features of tumor blood vessels for drug delivery, factors involved, and limitations and augmentation of the effect","volume":"63","author":"Fang","year":"2011","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.jconrel.2016.11.015","article-title":"To exploit the tumor microenvironment: Since the EPR effect fails in the clinic, what is the future of nanomedicine?","volume":"244","author":"Danhier","year":"2016","journal-title":"J. Control. Release"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1021\/bc9004365","article-title":"Transferrin receptor-targeted liposomes encapsulating anti-BCR-ABL siRNA or asODN for chronic myeloid leukemia treatment","volume":"21","author":"Firmino","year":"2010","journal-title":"Bioconjug. Chem."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1038\/nrc2368","article-title":"Getting to the stem of chronic myeloid leukaemia","volume":"8","author":"Savona","year":"2008","journal-title":"Nat. Rev. Cancer"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1016\/S1357-2725(99)00070-9","article-title":"The transferrin receptor: Role in health and disease","volume":"31","author":"Ponka","year":"1999","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1002\/med.10008","article-title":"Transferrin\/transferrin receptor-mediated drug delivery","volume":"22","author":"Li","year":"2002","journal-title":"Med. Res. Rev."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.clim.2006.06.010","article-title":"The transferrin receptor part I: Biology and targeting with cytotoxic antibodies for the treatment of cancer","volume":"121","author":"Daniels","year":"2006","journal-title":"Clin. Immunol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.clim.2006.06.006","article-title":"The transferrin receptor part II: Targeted delivery of therapeutic agents into cancer cells","volume":"121","author":"Daniels","year":"2006","journal-title":"Clin. Immunol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1056\/NEJMra013339","article-title":"Imatinib mesylate--a new oral targeted therapy","volume":"346","author":"Savage","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.critrevonc.2005.06.007","article-title":"Novel targeted therapies to overcome imatinib mesylate resistance in chronic myeloid leukemia (CML)","volume":"57","author":"Walz","year":"2006","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1002\/bit.22858","article-title":"Co-encapsulation of anti-BCR-ABL siRNA and imatinib mesylate in transferrin receptor-targeted sterically stabilized liposomes for chronic myeloid leukemia treatment","volume":"107","author":"Moreira","year":"2010","journal-title":"Biotechnol. Bioeng."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: The next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1083\/jcb.200304132","article-title":"Nucleolin expressed at the cell surface is a marker of endothelial cells in angiogenic blood vessels","volume":"163","author":"Christian","year":"2003","journal-title":"J. Cell Biol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"7444","DOI":"10.1073\/pnas.062189599","article-title":"A fragment of the HMGN2 protein homes to the nuclei of tumor cells and tumor endothelial cells in vivo","volume":"99","author":"Porkka","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.2217\/nnm.12.174","article-title":"Efficient intracellular delivery of siRNA with a safe multitargeted lipid-based nanoplatform","volume":"8","author":"Abasolo","year":"2013","journal-title":"Nanomedicine (London)"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.ijpharm.2012.05.018","article-title":"Toward a siRNA-containing nanoparticle targeted to breast cancer cells and the tumor microenvironment","volume":"434","author":"Santos","year":"2012","journal-title":"Int. J. Pharm."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.ejpb.2013.04.007","article-title":"Impact of anti-PLK1 siRNA-containing F3-targeted liposomes on the viability of both cancer and endothelial cells","volume":"85","author":"Ramalho","year":"2013","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/s10549-011-1688-7","article-title":"Targeted and intracellular triggered delivery of therapeutics to cancer cells and the tumor microenvironment: Impact on the treatment of breast cancer","volume":"133","author":"Moura","year":"2012","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.jconrel.2014.09.024","article-title":"Simultaneous active intracellular delivery of doxorubicin and C6-ceramide shifts the additive\/antagonistic drug interaction of non-encapsulated combination","volume":"196","author":"Fonseca","year":"2014","journal-title":"J. Control. Release"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.biomaterials.2015.08.007","article-title":"Nucleolin overexpression in breast cancer cell sub-populations with different stem-like phenotype enables targeted intracellular delivery of synergistic drug combination","volume":"69","author":"Fonseca","year":"2015","journal-title":"Biomaterials"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.cell.2013.06.005","article-title":"Poised chromatin at the ZEB1 promoter enables breast cancer cell plasticity and enhances tumorigenicity","volume":"154","author":"Chaffer","year":"2013","journal-title":"Cell"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"e100","DOI":"10.1038\/mtna.2013.30","article-title":"Tumor-targeted Chlorotoxin-coupled Nanoparticles for Nucleic Acid Delivery to Glioblastoma Cells: A Promising System for Glioblastoma Treatment","volume":"2","author":"Costa","year":"2013","journal-title":"Mol. Nucleic Acids"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.jconrel.2015.04.002","article-title":"MiRNA-21 silencing mediated by tumor-targeted nanoparticles combined with sunitinib: A new multimodal gene therapy approach for glioblastoma","volume":"207","author":"Costa","year":"2015","journal-title":"J. Control. Release"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"545","DOI":"10.15252\/emmm.201607199","article-title":"Delivery is key: Lessons learnt from developing splice-switching antisense therapies","volume":"9","author":"Godfrey","year":"2017","journal-title":"Embo. Mol. Med."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.nbd.2009.07.028","article-title":"Approaches to transport therapeutic drugs across the blood-brain barrier to treat brain diseases","volume":"37","author":"Gabathuler","year":"2010","journal-title":"Neurobiol. Dis."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1038\/sj.gt.3300674","article-title":"Gene delivery by negatively charged ternary complexes of DNA, cationic liposomes and transferrin or fusigenic peptides","volume":"5","author":"Slepushkin","year":"1998","journal-title":"Gene Ther."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"1798","DOI":"10.1038\/sj.gt.3301015","article-title":"Mechanisms of gene transfer mediated by lipoplexes associated with targeting ligands or pH-sensitive peptides","volume":"6","author":"Slepushkin","year":"1999","journal-title":"Gene Ther."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1002\/jlb.65.2.270","article-title":"Transfection of human macrophages by lipoplexes via the combined use of transferrin and pH-sensitive peptides","volume":"65","author":"Slepushkin","year":"1999","journal-title":"J. Leukoc. Biol."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/S0005-2736(99)00225-4","article-title":"Efficient gene transfer by transferrin lipoplexes in the presence of serum","volume":"1463","year":"2000","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.expneurol.2003.12.013","article-title":"Improving lipoplex-mediated gene transfer into C6 glioma cells and primary neurons","volume":"187","year":"2004","journal-title":"Exp. Neurol."},{"key":"ref_167","first-page":"1242","article-title":"Tf-lipoplex-mediated NGF gene transfer to the CNS: Neuronal protection and recovery in an excitotoxic model of brain injury","volume":"12","author":"Cardoso","year":"2005","journal-title":"Gene"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1002\/jgm.1006","article-title":"siRNA delivery by a transferrin-associated lipid-based vector: A non-viral strategy to mediate gene silencing","volume":"9","author":"Cardoso","year":"2007","journal-title":"J. Gene Med."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.jconrel.2008.08.014","article-title":"Tf-lipoplexes for neuronal siRNA delivery: A promising system to mediate gene silencing in the CNS","volume":"132","author":"Cardoso","year":"2008","journal-title":"J. Control. Release"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/j.jconrel.2009.11.004","article-title":"Tf-lipoplex-mediated c-Jun silencing improves neuronal survival following excitotoxic damage in vivo","volume":"142","author":"Cardoso","year":"2010","journal-title":"J. Control. Release"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.jconrel.2010.08.011","article-title":"RVG peptide tethered bioreducible polyethylenimine for gene delivery to brain","volume":"155","author":"Son","year":"2011","journal-title":"J. Control. Release"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1080\/1061186X.2016.1223676","article-title":"The potential use of rabies virus glycoprotein-derived peptides to facilitate drug delivery into the central nervous system: A mini review","volume":"25","author":"Huey","year":"2017","journal-title":"J. Drug Target."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.1007\/s11095-013-1068-6","article-title":"Cellular uptake mechanism and therapeutic utility of a novel peptide in targeted-delivery of proteins into neuronal cells","volume":"30","author":"Fu","year":"2013","journal-title":"Pharm. Res."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"2177","DOI":"10.1021\/acs.molpharmaceut.7b00158","article-title":"Targeting the Central Nervous System (CNS): A Review of Rabies Virus-Targeting Strategies","volume":"14","author":"Oswald","year":"2017","journal-title":"Mol. Pharm."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/448033a","article-title":"Molecular medicine: Entry granted","volume":"448","author":"Cantin","year":"2007","journal-title":"Nature"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1038\/nature05901","article-title":"Transvascular delivery of small interfering RNA to the central nervous system","volume":"448","author":"Kumar","year":"2007","journal-title":"Nature"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1002\/(SICI)1097-4598(200005)23:5<720::AID-MUS9>3.0.CO;2-5","article-title":"Rabies virus entry at the neuromuscular junction in nerve-muscle cocultures","volume":"23","author":"Lewis","year":"2000","journal-title":"Muscle Nerve"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"16148","DOI":"10.1074\/jbc.M114.549980","article-title":"Rabies virus envelope glycoprotein targets lentiviral vectors to the axonal retrograde pathway in motor neurons","volume":"289","author":"Hislop","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"2417","DOI":"10.1016\/j.biomaterials.2009.11.086","article-title":"Targeted nonviral delivery vehicles to neural progenitor cells in the mouse subventricular zone","volume":"31","author":"Kwon","year":"2010","journal-title":"Biomaterials"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.jns.2009.09.032","article-title":"Gene therapy using lactoferrin-modified nanoparticles in a rotenone-induced chronic Parkinson model","volume":"290","author":"Huang","year":"2010","journal-title":"J. Neurol. Sci."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.colsurfb.2011.08.001","article-title":"Dual targeted delivery of doxorubicin to cancer cells using folate-conjugated magnetic multi-walled carbon nanotubes","volume":"89","author":"Lu","year":"2012","journal-title":"Colloids Surf. B. Biointerfaces"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"5628","DOI":"10.1016\/j.biomaterials.2013.03.097","article-title":"Glioma targeting and blood-brain barrier penetration by dual-targeting doxorubincin liposomes","volume":"34","author":"Gao","year":"2013","journal-title":"Biomaterials"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"e1429","DOI":"10.1002\/wnan.1429","article-title":"Recent advances of using polyhydroxyalkanoate-based nanovehicles as therapeutic delivery carriers","volume":"9","author":"Li","year":"2016","journal-title":"Nanomed. Nanobiotechnol."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.jconrel.2016.01.046","article-title":"Doxorubicin-loaded nanoparticles consisted of cationic- and mannose-modified-albumins for dual-targeting in brain tumors","volume":"225","author":"Byeon","year":"2016","journal-title":"J. Control. Release"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.neo.2014.11.001","article-title":"Recombinant interleukin-1 receptor antagonist conjugated to superparamagnetic iron oxide nanoparticles for theranostic targeting of experimental glioblastoma","volume":"17","author":"Shevtsov","year":"2015","journal-title":"Neoplasia"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1007\/s11481-016-9698-1","article-title":"Advances in Targeted Drug Delivery Approaches for the Central Nervous System Tumors: The Inspiration of Nanobiotechnology","volume":"12","author":"Meng","year":"2017","journal-title":"J. Neuroimmune Pharm."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.biomaterials.2015.12.021","article-title":"Intravenous administration of brain-targeted stable nucleic acid lipid particles alleviates Machado-Joseph disease neurological phenotype","volume":"82","author":"Gomes","year":"2016","journal-title":"Biomaterials"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.bbamem.2009.12.001","article-title":"Design of peptide-targeted liposomes containing nucleic acids","volume":"1798","author":"Santos","year":"2010","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1038\/mt.2013.285","article-title":"Recombinant AAV as a platform for translating the therapeutic potential of RNA interference","volume":"22","author":"Borel","year":"2014","journal-title":"Mol. Ther."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/978-3-319-75402-4_12","article-title":"Gene Therapy Approaches to Treat the Neurodegeneration and Visual Failure in Neuronal Ceroid Lipofuscinoses","volume":"1074","author":"Smith","year":"2018","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_191","doi-asserted-by":"crossref","unstructured":"Haney, M.J., Zhao, Y., Jin, Y.S., and Batrakova, E.V. (2020). Extracellular Vesicles as Drug Carriers for Enzyme Replacement Therapy to Treat CLN2 Batten Disease: Optimization of Drug Administration Routes. Cells, 9.","DOI":"10.3390\/cells9051273"},{"key":"ref_192","first-page":"1113","article-title":"Delivery across the blood-brain barrier of antisense directed against amyloid beta: Reversal of learning and memory deficits in mice overexpressing amyloid precursor protein","volume":"297","author":"Banks","year":"2001","journal-title":"J. Pharm. Exp. Ther."},{"key":"ref_193","first-page":"948","article-title":"Imaging gene expression in the brain in vivo in a transgenic mouse model of Huntington\u2019s disease with an antisense radiopharmaceutical and drug-targeting technology","volume":"43","author":"Lee","year":"2002","journal-title":"J. Nucl. Med."},{"key":"ref_194","first-page":"340","article-title":"An aquaporin 4 antisense oligonucleotide loaded, brain targeted nanoparticulate system design","volume":"69","author":"Kozlu","year":"2014","journal-title":"Pharmazie"},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1186\/s13023-014-0180-y","article-title":"Therapeutic strategies based on modified U1 snRNAs and chaperones for Sanfilippo C splicing mutations","volume":"9","author":"Matos","year":"2014","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1038\/mt.2011.54","article-title":"Neuroblastoma-targeted nanoparticles entrapping siRNA specifically knockdown ALK","volume":"19","author":"Brignole","year":"2011","journal-title":"Mol. Ther."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/16\/5732\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:58:50Z","timestamp":1760176730000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/16\/5732"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,10]]},"references-count":196,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2020,8]]}},"alternative-id":["ijms21165732"],"URL":"https:\/\/doi.org\/10.3390\/ijms21165732","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,10]]}}}