Lentiviral Vectors for Gene Delivery to the Nervous System - Gene Delivery and Therapy for Neurological Disorders - page 32

Table 1
(continued)

Pseudotype envelope Tropism and other features References

Ross river virus (RRV) RRV-pseudotyped FIV vectors: effi cient transduction of
hepatocytes and Kupffer cells in the liver upon systemic
administration, neuroglial cells transduction (astrocytes
and oligodendrocytes) upon brain injection

[ 147 ]
[ 43 ]

Sendai virus (SEV F
and HN)

Transduction of apical surface airway epithelium. Human
hepatocytes.

[ 148 , 149 ]

Sindbis virus Can be used for cell specifi c targeting applications by

insertion of cell-specifi c ligands; able to pseudotype
oncoretroviruses and lentiviruses; effi cient gene-targeting
system based on antibody-mediated binding; effi cient
transduction of mouse liver and spleen cells upon
intravenous injection

[ 65 - 67 , 71 ,
150 ]

Venezuela equine
infectious virus

Mostly neurons than glial [ 151 ]

Vesicular stomatitis
virus (VSV)

Broad cell tropism; preferentially transduces neurons when
injected in the CNS

[ 53 ]
[ 152 ]
[ 59 ]

Concentration via ultracentrifugation [ 131 ]

Not retrograde transport; cytotoxicity; inactivation
by human serum

[ 145 ]

poses limitations and challenges for human application. The high
affi nity of some vectors in muscle, the architecture of nerves inner-
vating the distal extremities, and more importantly the muscle
mass, make intramuscular approach for treatment of motor neuron
diseases one of the biggest challenges. Alternatively, injections into
the peripheral nervous system have been attempted. Indeed Tanase
et al. reported rabies-G EIAV gene expression in cervical spinal
cord motor neurons in a mouse model upon brachial plexus injec-
tion [ 45 ]. However, the restricted access at synaptic terminals,
which restricts both neuronal uptake and axonal transport, is a lim-
iting factor for the application of this method in humans.

1.7 Cell Type-
Specifi c Targeting

A desired gene therapy protocol would be to precisely deliver a
gene of interest to specifi c cells in vivo using a targeted gene deliv-
ery vehicle for administration. As an alternative to pseudotyping
with existing envelopes, various modifi cations have been employed
to improve the targeting of vectors to specifi c cell types and regu-
late transgene expression.