Intrathecal Injection of Newborn Mouse for GenomeEditing and Drug Delivery
Journal of visualized experiments : JoVE(2024)
Abstract
Intrathecal injection is a commonly employed procedure in both pediatric and adultclinics, serving as an effective means to administer medications and treatments.By directly delivering medications and treatments into the cerebrospinal fluid of thecentral nervous system, this method achieves higher localized drug concentrationswhile reducing systemic side-effects compared to other routes such as intravenous,subcutaneous, or intramuscular injections. Its importance extends beyond clinicalsettings, as intrathecal injection plays a vital role in preclinical studies focused ontreating neurogenetic disorders in rodents and other large animals, including non-human primates. However, despite its widespread application, intrathecal injectionin young, particularly neonatal pups, poses significant technical challenges dueto their small size and fragile nature. Successful and reliable administration ofintrathecal injections in newborn mice requires meticulous attention to detail andcareful consideration of various factors. Thus, there is a crucial need for a standardizedprotocol that not only provides instructions but also highlights key technicalconsiderations and good laboratory practices to ensure procedural consistency, aswell as the safety and welfare of the animals. To address this unmet need, we present a detailed and comprehensive protocolfor performing intrathecal injections specifically in newborn pups on postnatal day1 (P1). By following the step-by-step instructions, researchers can confidentlyperform intrathecal injections in neonatal pups, enabling the accurate delivery ofdrugs, antisense oligos, and viruses for gene replacement or genome editing-basedtreatments. Furthermore, the importance of adhering to good laboratory practices isemphasized to maintain the well-being of animals and ensure reliable experimentaloutcomes. This protocol aims to address the technical challenges associated with intrathecal injections in neonatal mice, ultimately facilitating advances in the field ofneurogenetic research that aims to develop potential therapeutic interventions
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