Biomedical Engineering Reference
In-Depth Information
retrovirus vectors (RV) containing a transgene, which will infect
nearby neighbor cells. Such a vector can efficiently “propagate” the
transgene after transfection with synthetic vectors. This system is
especially suited for suicide gene strategies [17]. Finally, the advent
of small interfering RNA (siRNA), a class of double-stranded RNA
nucleotides composed of 20-25 bases, with a variety of roles in
biology, is involved in the RNA interference (RNAi) pathway, where
it interferes with the expression of a specific gene [18]. Therefore,
siRNA can be used for treating genetic diseases mediated by a
pathogenic protein that, once silenced by an appropriate siRNA, can
be palliated. An advantage of siRNA is that its low molecular weight
allows a better bioavailability as compared to plasmid DNA and its
complexion with synthetic gene delivery carriers improves its bio-
stability.
In general, complexes formed between the positively charged
synthetic vectors and the negatively charged genetic material
(either plasmid DNA or siRNA) are mostly characterized as being
nanometric multi-lamellar bilayer particles (see Fig. 1.1).
C
Figure 1.1
Schematic of two distinct pathways from the lamellar L
phase
α
C
to the columnar inverted hexagonal H
phase of cationic lipid-
DNA complexes. Along pathway I, the natural curvature C
II
5
o
1/R
of the cationic lipid monolayer is driven negative by the
addition of the helper-lipid DOPE. This is shown schematically
(center top); the cationic lipid DOTAP is cylindrically shaped
whereas DOPE is cone-like, leading to the negative curvature.
Along pathway II, the L
o
C
C
transition is induced by the
addition of helper-lipids consisting of mixtures of DOPC and the
co-surfactant hexanol, which reduces the membrane bending
rigidity. This figure was reproduced with permission [19].
→
H
α
II
Search WWH ::
Custom Search