Biomedical Engineering Reference
In-Depth Information
effective in achieving high efficiency for both gene delivery and expression.
Nevertheless, the limitations associated with viral vectors, including immuno-
genic responses, risk of tumorigenicity, complicated preparation, and high
cost, have encouraged researchers to investigate and develop safe and efficient
nonviral gene delivery vehicles.
2
The advantages of nonviral systems are obvious. Besides their lesser toxicity
and lower immune responses than viral vectors, no integration into the host
genome occurs during nonviral vector-mediated gene delivery. Moreover,
nonviral methods are not limited by the size of the gene cargo, are stable to
storage, are easier to produce on a large scale, and can offer remarkable
structural and chemical versatility. Nonviral gene vectors can be broadly
categorized into polymers, liposomes, peptides, and organic/inorganic
nanoparticles.
3
Especially, cationic polymer vectors have been considered as
the most common DNA condensing agents. They interact with negatively
charged plasmid DNA through electrostatic interactions and package them
into nanoscale polyplexes, which can protect DNA from enzymatic
degradation and transport the gene into target cells through an endocytic
pathway (Figure 4.2).
In order to achieve maximum expression of a therapeutic gene carried by
vectors, multiple hurdles must be overcome.
4
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n
4
y
3
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g
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3
These include (1) protection of
the
complexes from
in vivo degradation; (2) efficient transfection of
the
complexes
into
the
target
cell;
(3)
protection/prevention
from
nuclease
Figure 4.1
In vivo and ex vivo gene therapy. (1) During the in vivo process, vector-
mediated therapeutic genes are injected into the patient and transfected
directly. (2) During the ex vivo process, therapeutic genes are first inserted
into cells in vitro. The transfected cells are then expanded and reimplanted
into the patient.
