Biomedical Engineering Reference
In-Depth Information
resulted in effective immunization of the animal against infl uenza. Similar results, using other
pathogen models, have also now been generated. It is assumed that expressed antigen is secreted
by the cell and, in this way, is exposed to immune surveillance.
Further research has illustrated that systematic administration via i.v. injection rarely achieves
meaningful cell transfection. This is most likely due to the high nuclease levels present in serum.
In contrast, free nuclease activity in muscle tissue is extremely low.
Modern non-viral-based systems generally entail complexing/packaging the gene of interest
(present, along with appropriate promoters, etc., in a circular plasmid) with additional molecules,
particularly various lipids or some polypeptides. These generally display a positive charge and,
hence, interact with the negatively charged DNA molecules. The function of such carrier mol-
ecules is to stabilize the DNA, protect it from, for example, serum nucleases and ideally to modu-
late interaction with the biological system (e.g. help target the DNA to particular cell types, or
away from other cell types).
The most commonly used polymers are the cationic lipids and polylysine chains (Figure 14.8).
Cationic lipids can aggregate in aqueous-based systems to form vesicles/liposomes, which in turn
CH
3
O
C
18
H
35
+
N
+
N
CH
3
(CH
2
)
15
CH
3
CH
O
C
18
H
35
CH
3
DOTMA
CTAB
CH
3
(CH
2
)
13
CH
3
O
+
N
HO
CH
2
CH
2
CH
2
CH
CH
2
O
(CH
2
)
15
CH
3
CH
3
DMRI
O
+
NH
3
COO
-
CH
C
NH
CH
(CH
2
)
4
(CH
2
)
4
+
NH
3
+
NH
3
n
Polylysine
Figure 14.8
Structure of some cationic lipids and polylysine
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