Cerebellomedullary Cistern Injection of Viral Vectors in Nonhuman Primates

  • Lluis SamaranchEmail author
  • Kousaku Ohno
  • Waldy San Sebastian
  • Krystof Bankiewicz
Part of the Methods in Molecular Biology book series (MIMB, volume 1937)


Gene therapy shows great promise for the treatment of neurological disorders, and accessing cerebrospinal fluid (CSF) from the cerebellomedullary cistern through the posterior atlanto-occipital membrane has become a common route of delivery in preclinical studies. Unlike direct brain parenchymal infusions, CSF delivery offers broader coverage to the central and peripheral nervous system. This prospectively increases its translational value, more specially to treat global brain dysfunctions in which the pathology is disseminated throughout the brain and not focalized in one specific brain structure. Also, from the practical point of view, this approach offers a more reliable method for neurological gene replacement in infants, whose immature cranial suture preclude the use of skull-mounted devices. Here we describe a consistent, precise, and safe method for CSF injection.

Key words

CSF delivery Gene therapy Viral vector Nonhuman primates Preclinical research 



This work was supported by a grant to K.S.B. from NIH-NINDS (R01NS073940-01).


  1. 1.
    Foust KD, Nurre E, Montgomery CL et al (2009) Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes. Nat Biotechnol 27:59–65. Scholar
  2. 2.
    Samaranch L, Salegio EA, San Sebastian W et al (2013) Strong cortical and spinal cord transduction after AAV7 and AAV9 delivery into the cerebrospinal fluid of nonhuman primates. Hum Gene Ther 24:526–532. Scholar
  3. 3.
    Samaranch L, Salegio EA, San Sebastian W et al (2012) Adeno-associated virus serotype 9 transduction in the central nervous system of nonhuman primates. Hum Gene Ther 23:382–389. Scholar
  4. 4.
    Salegio EA, Streeter H, Dube N et al (2014) Distribution of nanoparticles throughout the cerebral cortex of rodents and non-human primates: implications for gene and drug therapy. Front Neuroanat 8:9. Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Lluis Samaranch
    • 1
    Email author
  • Kousaku Ohno
    • 1
  • Waldy San Sebastian
    • 1
  • Krystof Bankiewicz
    • 1
  1. 1.Department of Neurological SurgeryUniversity of California San FranciscoSan FranciscoUSA

Personalised recommendations