Slow Infusion of Recombinant Adeno-Associated Viruses into the Mouse Cerebrospinal Fluid Space

Hum Gene Ther Methods. 2018 Apr;29(2):75-85. doi: 10.1089/hgtb.2017.250. Epub 2018 Mar 29.

Abstract

Recombinant adeno-associated viruses (rAAVs) are the leading in vivo gene delivery platform, and have been extensively studied in gene therapy targeting various tissues, including the central nervous system (CNS). A single-bolus rAAV injection to the cerebrospinal fluid (CSF) space has been widely used to target the CNS, but it suffers from several drawbacks, such as leakage to peripheral tissues. Here, a protocol is described using an osmotic pump to infuse rAAV slowly into the mouse CSF space. Compared to the single-bolus injection technique, pump infusion can lead to higher CNS transduction and lower transduction in the peripheral tissues.

Keywords: adeno-associated virus; central nervous system; gene therapy; intrathecal delivery.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Brain / metabolism
  • Brain / surgery
  • Brain / virology
  • Catheters, Indwelling
  • Cerebrospinal Fluid / virology
  • Dependovirus / genetics*
  • Dependovirus / metabolism
  • Female
  • Genetic Therapy / methods
  • Genetic Vectors / administration & dosage*
  • Humans
  • Infusion Pumps, Implantable
  • Infusions, Intraventricular
  • Infusions, Spinal / instrumentation
  • Infusions, Spinal / methods*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Osmotic Pressure
  • Spinal Cord / metabolism
  • Spinal Cord / surgery*
  • Spinal Cord / virology
  • Transduction, Genetic / instrumentation
  • Transduction, Genetic / methods*
  • Transgenes