Herpes Simplex Virus 1 (HSV-1)-Based Vectors - Viral Vector Approaches in Neurobiology and Brain Diseases - page 67

Ataxias Neurodegenerative diseases

AD (133, 134, 139)
PD (135,143-150, 151, 152)
Narcolepsy (155)

Neuroprotection
Neurotrophins (156-162)
Apoptosis and HSP (163-170)
Antioxidants (176-178)

Brain tumours
Toxic proteins (179, 180, 183)
Pro-apoptic proteins
(187-191)

FA (119-113)
AT (122-124)

Disease models

Amplicon vectors in Neurosciences
(reviews 18, 19, 114-116)

Complex neural functions

Learning and memory
NMDAR NR1 (139, 140, 193,194)

Fear conditioning
AMPA GluR1 (196)
CREB (197, 198)

Food preference and
social interactions
CREB (199-201)

Alcoholism
GABA (202)

Fig. 7 Applications of amplicon vectors. The numbers in square brackets refer to the list of references

regulatory sequences or combination of several genes could be
delivered using these vectors; (3) widespread cellular tropism:
though naturally HSV-1 infects mainly neurons and epithelial cells,
amplicons can experimentally infect a wide range of cell types
including glial cells; and (4) since the viral genome does not inte-
grate into cellular chromosomes, there is very low probability to
induce insertional mutagenesis. The last two features are shared
with recombinant defective HSV-1 vectors.
Several recent technological breakthroughs addressing both
the possibility to produce large amounts of helper-free amplicon
vectors [ 28 , 29 ] and the ability to deliver very large pieces of for-
eign DNA [ 117 , 118 ] have, amongst other improvements, signifi -
cantly favored the application of these vectors in different settings
of experimental gene therapy models and for the study of complex
neural functions. Recent applications of gene transfer into the
brain using amplicon vectors (Fig. 7 ) have focused on (1) experi-
mental gene therapy of inherited genetic diseases affecting the ner-
vous system such as ataxias, (2) neurodegenerative disorders, using
experimental models of Parkinson's disease or Alzheimer's disease,
(3) neuroprotection and synapse restoration, (4) brain cancer, and
(5) a group of complex functions of the nervous system related
to anxiety, sexual behavior, and learning and memory in animal
models, using different tasks such as fear conditioning and inhibi-
tory avoidance paradigms.

The capacity of amplicons to deliver very large DNA fragments
was used to treat an experimental model of Friedreich's ataxia

14.1 Ataxias