Satti Medha, Prasad Kavita, Patel Yash, Poulathas Demi, Walker Lawrence, Paghdal Esha, Gunderson Samuel, Yu Lei
Department of Genetics, Rutgers University, Piscataway, NJ, 08854, USA.
Center of Alcohol & Substance Use Studies, Rutgers University, Piscataway, NJ, 08854, USA.
Curr Res Pharmacol Drug Discov. 2025 Apr 17;8:100220. doi: 10.1016/j.crphar.2025.100220. eCollection 2025.
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.
U1衔接子是一种新型基因沉默技术，为中枢神经系统（CNS）中的靶基因治疗疾病提供了一种创新方法。鞘内给药是中枢神经系统靶向核酸药物的一种医学可行给药途径；因此，研究鞘内给药后U1衔接子的分布很重要。我们研究了小鼠鞘内推注给药后U1衔接子的分布模式。它很容易分布到中枢神经系统组织，包括腰段和颈段脊髓以及小脑。随着时间的推移，U1衔接子也在外周组织中积累，包括肝脏和肾脏，而血浆中检测不到其水平。我们的研究结果为未来深入开展鞘内给药后U1衔接子分布的药代动力学建模提供了有用信息。
