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Updated: Apr 28, 2026
Expansion of Embryonic and Adult Neural Stem Cells by In Utero Electroporation or Viral Stereotaxic Injection
Published on: October 6, 2012
Titer and product affect the distribution of gene expression after intraputaminal convection-enhanced delivery
Marina E Emborg1, Samuel A Hurley, Valerie Joers
1Preclinical Parkinson's Research Program, Wisconsin National Primate Research Center, University of Wisconsin, Madison, Wis., USA.
Background:
The efficacy and safety of intracerebral gene therapy for brain disorders like Parkinson's disease depends on the appropriate distribution of gene expression.
Objectives:
To assess whether the distribution of gene expression is affected by vector titer and protein type.
Methods:
Four adult macaque monkeys seronegative for adeno-associated virus 5 (AAV5) received a 30-µl inoculation of a high- or a low-titer suspension of AAV5 encoding glial cell line-derived neurotrophic factor (GDNF) or green fluorescent protein (GFP) in the right and left ventral postcommissural putamen. The inoculations were conducted using convection-enhanced delivery and intraoperative MRI (IMRI).
Results:
IMRI confirmed targeting and infusion cloud irradiation from the catheter tip into the surrounding area. A postmortem analysis 6 weeks after surgery revealed GFP and GDNF expression ipsilateral to the injection site that had a titer-dependent distribution. GFP and GDNF expression was also observed in fibers in the substantia nigra (SN) pars reticulata (pr), demonstrating anterograde transport. Few GFP-positive neurons were present in the SN pars compacta (pc), possibly by direct retrograde transport of the vector. GDNF was present in many neurons of the SNpc and SNpr.
Conclusions:
After controlling for target and infusate volume, the intracerebral distribution of the gene product was affected by the vector titer and product biology.
