Affiliations: Biovex Ltd, Windeyer Building, Cleveland Street,
London, UK | Department of Anatomy and Developmental Biology,
University College London, Gower Street, London, UK
Note: [] Corresponding author: Dr G. Campbell, Department of Cell
& Developmental Biology, University College London, Gower Street,
London, WC1E 6BT, UK. Tel.: +44 020 7679 7764; Fax: +44 020 7679 7349; E-mail:
[email protected]
Abstract: Purpose: The primary motor pathway, the corticospinal tract, is a
major target for spinal cord regeneration studies. One way of improving the
regeneration of corticospinal axons is to introduce regeneration-associated
genes into cortical motor neurons using viral vector delivery. Methods: We used an engineered Herpes Simplex virus (HSV1)
with the EF1α promoter encoding either LacZ or GFP to transduce
cortical neurons through retrograde transport following the injection of vector
into adult rat striatum or spinal cord. After three-days to one-month
post-injection, sections of brain and spinal cord were viewed with fluorescence
microscopy or processed for LacZ histochemistry. Results: Many layer V motor cortical neurons were transduced
following striatal injections. These were not corticospinal neurons as they
were not fluorogold-labelled following tracer injection into spinal cord.
Corticospinal neurons in both hemispheres were, however, transduced following
direct vector injections into the dorsal column of spinal cord, yielding
250–400 transduced corticospinal neurons per animal. No non-pyramidal neurons
or thalamic neurons were transduced by spinal injections. Conclusions: Therefore, this HSV1.EF1α vector is
highly effective for the transduction of corticospinal neurons without direct
injection into the brain and could be used to introduce regeneration-relevant
genes into these neurons with the aim of regenerating the corticospinal
tract.
Keywords: In vivo transduction, corticospinal neurons, HSV1 vector, elongation factor 1α, rat
