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Lumbar Intrathecal Injection of Gene Therapy Vectors for Central Nervous System Targeting in Mice and Rats
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Efficient CNS gene delivery by intravenous injection.

Jean-Pierre Louboutin1, Alena A Chekmasova, Elena Marusich

  • 1Department of Pathology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA. jplouboutin@hotmail.com

Nature Methods
|October 19, 2010
PubMed
Summary

Recombinant simian virus 40-derived viral vectors (rSV40s) enable gene delivery to the central nervous system (CNS). Mannitol pretreatment significantly enhances rSV40s

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Published on: June 23, 2011

Area of Science:

  • Neuroscience
  • Gene Therapy
  • Viral Vector Technology

Background:

  • Central nervous system (CNS) gene delivery is challenging.
  • Simian virus 40 (SV40)-derived viral vectors (rSV40s) are potential tools for CNS gene therapy.
  • Mannitol is a hyperosmotic agent that can alter biological barriers.

Purpose of the Study:

  • To evaluate the efficacy of intravenous rSV40 administration for CNS gene delivery.
  • To investigate the effect of mannitol pretreatment on rSV40-mediated CNS gene delivery.

Main Methods:

  • Recombinant SV40-derived viral vectors (rSV40s) were administered intravenously to mice.
  • Mice received either no pretreatment or intraperitoneal injection of mannitol prior to rSV40 administration.
  • Transgene expression in the CNS was detected and quantified.

Main Results:

  • Transgene-expressing cells, predominantly neurons, were found in the cortex and spinal cord.
  • Prior intraperitoneal mannitol injection increased CNS gene delivery by tenfold.
  • Intravenous rSV40s with mannitol pretreatment led to extensive transgene expression throughout the CNS.

Conclusions:

  • Intravenous rSV40s are effective for delivering transgenes to the CNS.
  • Mannitol pretreatment significantly enhances rSV40-mediated gene delivery to the CNS.
  • This method holds promise for CNS gene therapy applications.