Tissue distribution pharmacokinetics of intrathecal U1 adaptor oligonucleotide in mice
U1 Adaptor is a novel gene-silencing technology, offering an innovative approach to target genes in the CNS for the treatment of diseases. Intrathecal delivery is a medically viable route of administration of CNS-bound nucleic acid drugs; therefore, it is important to investigate U1 Adaptor distribu...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-01-01
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| Series: | Current Research in Pharmacology and Drug Discovery |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590257125000082 |
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| author | Medha Satti Kavita Prasad Yash Patel Demi Poulathas Lawrence Walker Esha Paghdal Samuel Gunderson Lei Yu |
| author_facet | Medha Satti Kavita Prasad Yash Patel Demi Poulathas Lawrence Walker Esha Paghdal Samuel Gunderson Lei Yu |
| author_sort | Medha Satti |
| collection | DOAJ |
| description | U1 Adaptor is a novel gene-silencing technology, offering an innovative approach to target genes in the CNS for the treatment of diseases. Intrathecal delivery is a medically viable route of administration of CNS-bound nucleic acid drugs; therefore, it is important to investigate U1 Adaptor distribution after intrathecal drug delivery. We investigated the distribution patterns of U1 Adaptor upon intrathecal bolus administration in mice. It readily distributes to CNS tissues, including the lumbar and the cervical spinal cord, and the cerebellum. Over time, the U1 Adaptor also accumulates in the periphery, both in the liver and the kidneys, while plasma levels are undetectable. Our findings provide useful information for future in-depth pharmacokinetic modeling of U1 Adaptor distribution upon intrathecal administration. |
| format | Article |
| id | doaj-art-bbb427b04c8746aaa55baeba479a83dc |
| institution | DOAJ |
| issn | 2590-2571 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Current Research in Pharmacology and Drug Discovery |
| spelling | doaj-art-bbb427b04c8746aaa55baeba479a83dc2025-08-20T03:14:59ZengElsevierCurrent Research in Pharmacology and Drug Discovery2590-25712025-01-01810022010.1016/j.crphar.2025.100220Tissue distribution pharmacokinetics of intrathecal U1 adaptor oligonucleotide in miceMedha Satti0Kavita Prasad1Yash Patel2Demi Poulathas3Lawrence Walker4Esha Paghdal5Samuel Gunderson6Lei Yu7Department of Genetics, Rutgers University, Piscataway, NJ, 08854, USA; Center of Alcohol & Substance Use Studies, Rutgers University, Piscataway, NJ, 08854, USADepartment of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ, USADepartment of Genetics, Rutgers University, Piscataway, NJ, 08854, USA; Center of Alcohol & Substance Use Studies, Rutgers University, Piscataway, NJ, 08854, USADepartment of Genetics, Rutgers University, Piscataway, NJ, 08854, USA; Center of Alcohol & Substance Use Studies, Rutgers University, Piscataway, NJ, 08854, USADepartment of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ, USADepartment of Genetics, Rutgers University, Piscataway, NJ, 08854, USA; Center of Alcohol & Substance Use Studies, Rutgers University, Piscataway, NJ, 08854, USADepartment of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ, USA; Corresponding author.Department of Genetics, Rutgers University, Piscataway, NJ, 08854, USA; Center of Alcohol & Substance Use Studies, Rutgers University, Piscataway, NJ, 08854, USA; Corresponding author. Department of Genetics, Rutgers University, Piscataway, NJ, 08854, USA.U1 Adaptor is a novel gene-silencing technology, offering an innovative approach to target genes in the CNS for the treatment of diseases. Intrathecal delivery is a medically viable route of administration of CNS-bound nucleic acid drugs; therefore, it is important to investigate U1 Adaptor distribution after intrathecal drug delivery. We investigated the distribution patterns of U1 Adaptor upon intrathecal bolus administration in mice. It readily distributes to CNS tissues, including the lumbar and the cervical spinal cord, and the cerebellum. Over time, the U1 Adaptor also accumulates in the periphery, both in the liver and the kidneys, while plasma levels are undetectable. Our findings provide useful information for future in-depth pharmacokinetic modeling of U1 Adaptor distribution upon intrathecal administration.http://www.sciencedirect.com/science/article/pii/S2590257125000082U1 adaptorsGene silencingCentral nervous systemIntrathecal administrationPharmacokinetics |
| spellingShingle | Medha Satti Kavita Prasad Yash Patel Demi Poulathas Lawrence Walker Esha Paghdal Samuel Gunderson Lei Yu Tissue distribution pharmacokinetics of intrathecal U1 adaptor oligonucleotide in mice Current Research in Pharmacology and Drug Discovery U1 adaptors Gene silencing Central nervous system Intrathecal administration Pharmacokinetics |
| title | Tissue distribution pharmacokinetics of intrathecal U1 adaptor oligonucleotide in mice |
| title_full | Tissue distribution pharmacokinetics of intrathecal U1 adaptor oligonucleotide in mice |
| title_fullStr | Tissue distribution pharmacokinetics of intrathecal U1 adaptor oligonucleotide in mice |
| title_full_unstemmed | Tissue distribution pharmacokinetics of intrathecal U1 adaptor oligonucleotide in mice |
| title_short | Tissue distribution pharmacokinetics of intrathecal U1 adaptor oligonucleotide in mice |
| title_sort | tissue distribution pharmacokinetics of intrathecal u1 adaptor oligonucleotide in mice |
| topic | U1 adaptors Gene silencing Central nervous system Intrathecal administration Pharmacokinetics |
| url | http://www.sciencedirect.com/science/article/pii/S2590257125000082 |
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