The DOI matches its Crossref record; 55 of the 56 references it cites were found in a registry or an index.
Pharmacology of a Central Nervous System Delivered 2′-O-Methoxyethyl–Modified Survival of Motor Neuron Splicing Oligonucleotide in Mice and Nonhuman Primates
Open accessAbstract
Spinal muscular atrophy (SMA) is a debilitating neuromuscular disease caused by the loss of survival of motor neuron (SMN) protein. Previously, we demonstrated that ISIS 396443, an antisense oligonucleotide (ASO) targeted to the SMN2 pre-mRNA, is a potent inducer of SMN2 exon 7 inclusion and SMN protein expression, and improves function and survival of mild and severe SMA mouse models. Here, we demonstrate that ISIS 396443 is the most potent ASO in central nervous system (CNS) tissues of adult mice, compared with several other chemically modified ASOs. We evaluated methods of ISIS 396443 delivery to the CNS and characterized its pharmacokinetics and pharmacodynamics in rodents and nonhuman primates (NHPs). Intracerebroventricular bolus injection is a more efficient method of delivering ISIS 396443 to the CNS of rodents, compared with i.c.v. infusion. For both methods of delivery, the duration of ISIS 396443-mediated SMN2 splicing correction is long lasting, with maximal effects still observed 6 months after treatment discontinuation. Administration of ISIS 396443 to the CNS of NHPs by a single intrathecal bolus injection results in widespread distribution throughout the spinal cord. Based upon these preclinical studies, we have advanced ISIS 396443 into clinical development.
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“Many modifications can be applied to microRNA inhibitors and mimics, improving their stability, permeability, and specificity.”
From MiR-128-3p – a gray eminence of the human central nervous system (2024) · cites this paper as [195]
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“intrathecal ASO injection to nonhuman primates led to accumulation of ASO in the cortical neuronal and glial cells (Rigo et al., 2014).”
From microRNA-33 Regulates ApoE Lipidation and Amyloid-β Metabolism in the Brain (2015) · cites this paper as Rigo et al., 2014
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“Notably, intrathecal antisense oligonucleotides (ASO) injection successfully delivered ASO to the cortical cells in nonhuman primates [142].”
From MicroRNAs in brain cholesterol metabolism and their implications for Alzheimer's disease (2016) · cites this paper as [142]
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1 retracted
Foust, K. D., Wang, X., McGovern, V. L., Braun, L., Bevan, A. K., Haidet, A. M., Le, T. T., Morales, P. R., Rich, M. M., Burghes, A. H. M., et al. (2010) · Nature Biotechnology · doi:10.1038/nbt.1610 · Cited by 688
RetractedIdentification and characterization of a spinal muscular atrophy-determining gene
Lefebvre, S., Bürglen, L., Reboullet, S., Clermont, O., Burlet, P., Viollet, L., Bénichou, B., Cruaud, C., Millasseau, P., Zeviani, M., et al. (1995) · Cell · doi:10.1016/0092-8674(95)90460-3 · Cited by 3,995
Lorson, C. L., Hahnen, E., Androphy, E. J., & Wirth, B. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.11.6307 · Cited by 1,536
Bennett, C. F., & Swayze, E. E. (2010) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.010909.105654 · Cited by 1,431
Self-citationCorrelation between severity and SMN protein level in spinal muscular atrophy
Lefebvre, S., Burlet, P., Liu, Q., Bertrandy, S., Clermont, O., Münnich, A., Dreyfuss, G., & Melki, J. (1997) · Nature Genetics · doi:10.1038/ng0797-265 · Cited by 1,100
Lunn, M. R., & Wang, C. H. (2008) · The Lancet · doi:10.1016/s0140-6736(08)60921-6 · Cited by 1,010
Feldkötter, M., Schwarzer, V., Wirth, R., Wienker, T. F., & Wirth, B. (2002) · The American Journal of Human Genetics · doi:10.1086/338627 · Cited by 1,005
Monani, U. R. (1999) · Human Molecular Genetics · doi:10.1093/hmg/8.7.1177 · Cited by 951
Kordasiewicz, H. B., Stanek, L. M., Wancewicz, E. V., Mazur, C., McAlonis, M. M., Pytel, K. A., Artates, J. W., Weiss, A., Cheng, S. H., Shihabuddin, L. S., et al. (2012) · Neuron · doi:10.1016/j.neuron.2012.05.009 · Cited by 770
Self-citationMonani, U. R. (2000) · Human Molecular Genetics · doi:10.1093/hmg/9.3.333 · Cited by 745
Cited by
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Finkel, R. S., Chiriboga, C. A., Vajsar, J., Day, J., Montes, J., Vivo, D. C. D., Yamashita, M., Rigo, F., Hung, G., Schneider, E., et al. (2016) · The Lancet · doi:10.1016/s0140-6736(16)31408-8 · Cited by 1,039
Self-citationPharmacokinetics, biodistribution and cell uptake of antisense oligonucleotides
Geary, R. S., Norris, D. A., Yu, R. Z., & Bennett, C. F. (2015) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2015.01.008 · Cited by 866
Self-citationCrooke, S. T., Witztum, J. L., Bennett, C. F., & Baker, B. F. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.03.004 · Cited by 841
Self-citationPatient-Customized Oligonucleotide Therapy for a Rare Genetic Disease
Kim, J., Hu, C., Achkar, C. M. E., Black, L. E., Douville, J., Larson, A. A., Pendergast, M. K., Goldkind, S. F., Lee, E. A., Kuniholm, A., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1813279 · Cited by 852
Antisense oligonucleotides: the next frontier for treatment of neurological disorders
Rinaldi, C., & Wood, M. J. A. (2018) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.148 · Cited by 788
Metadata
- Authors
- Rigo, F., Chun, S. J., Norris, D. A., Hung, G., Lee, S., Matson, J., Fey, R. A., Gaus, H., Hua, Y., Grundy, J. S., Krainer, A. R., Henry, S. P., & Bennett, C. F.
- Affiliations
- Cold Spring Harbor Laboratory (US)
- ORCID
- Venue
- The Journal of Pharmacology and Experimental Therapeutics
- Publisher
- Elsevier BV
- Published
- 2014-07
- Volume
- 350
- Issue
- 1
- Pages
- 46-55
- ISSN
- 0022-3565 (ISSN-L)
- PMC
- PMC4056267
- OpenAlex
- W2090804804
- Cited by
- 283
- References
- 56
- Citations by year
- 2026: 16 · 2025: 19 · 2024: 22 · 2023: 25 · 2022: 24 · 2021: 25 · 2020: 35 · 2019: 24 · 2018: 23 · 2017: 23 · 2016: 21 · 2015: 21 · 2014: 5
- FWCI
- 11.71
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- Funders
- Spinal Muscular Atrophy Foundation
- National Institute of General Medical Sciences (R37-GM42699, R37GM042699, R01GM042699)
- Topics
- Health Sciences › Medicine › Genetics (clinical) › Neurogenetic and Muscular Disorders Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Health Sciences › Medicine › Clinical Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- spinal muscular atrophy, antisense oligonucleotides, SMN protein, central nervous system delivery, intrathecal administration, pharmacokinetics, pharmacodynamics, non-human primates, modified oligonucleotides, preclinical pharmacology
- MeSH terms
- Animals, Brain, Female, Injections, Intraventricular, Macaca fascicularis, Male, Muscular Atrophy, Spinal, Oligonucleotides, RNA Splicing, Mice, Knockout, Oligodeoxyribonucleotides, Antisense, Mice, Survival of Motor Neuron 2 Protein, Infusions, Intraventricular
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