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the coxsackie and adenovirus receptor (CAR). The RGD (Arg-Gly-Asp)
polypeptide loop that extends the penton is responsible for Ad binding to
its secondary cell receptors (integrins
α
b
α
b
), which triggers its
internalization (Rux & Burnett, 2004; San Martin & Burnett, 2003).
and
v
3
v
5
Figure 2.12
(Ad) structure. Ads have an icosahedral
morphology with a core diameter of 60-90 nm and possess a flexible fiber trimer
extending 32 nm from each of the 12 vertices. The viral capsid consists of three major
proteins: hexon, penton, and fiber, in addition to several proteins, such as pIX, that
stabilize hexon and penton. In the left-hand-side picture, a false-colored electron
micrograph image of an Ad is shown. Hexon is clearly visible (in green). Sites of
penton are identified in blue, and a single fiber is apparent (upper-left corner, in
red). The schematic illustration of the viral structure (on the right) shows the relative
positions of the capsid proteins for which specific engineering strategies have been
developed. The sites that are most suitable for incorporating novel peptide sequences
into the capsid structure through genetic engineering are highlighted. These include
the hexon hypervariable region (HVR), the penton Arg-Gly-Asp (RGD) loop, the pIX
carboxyl terminal, and the fiber knob carboxyl terminal and HI loop. Reproduced
with permission from Singh, R., and Kostarelos, K. (2009) Designer
Representation of the
Adenovirus
Adenoviruses
for
nanomedicine and nanodiagnostics,
Trends Biotechnol
.,
27
(4), 220-229.
Recombinant Ad vectors along with adeno-associated virus
(AAV) vectors (2.2.13) and
Gene therapy.
have been extensively
developed and utilized for therapeutic gene delivery. Gene therapy refers to the
correction of a defective gene by insertion of complementary gene functions
into cells and tissues to treat a disease. A normal gene may be delivered to
replace a non-functional gene and is commonly used to treat a hereditary
disease. Ad-based vectors have been the platform of choice for many years
for various reasons: Ad vectors are highly efficient for transfecting cells (the
Lentivirus
-based vectors
2
2
family. As such, its charac-
teristics are transfer and integration of large DNA segments into the host genome. Together with
Ads, it is one of the most efficient gene-delivery vectors.
Lentivirus
is also a mammalian virus; it is member of the
Retroviridae
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