Biomedical Engineering Reference
In-Depth Information
H
H
N
C
CO
x
CH
2
CH
2
CH
2
CH
2
NH
2
Poly-L-Lysine
H
CH
2
CH
2
x
DOTAP (cationic lipid)
DMRIE (cationic lipid)
Linear polyethlyenimine
H
2
N
NH
2
NH
2
H
2
N
N
N
NH
NH
NH
2
H
2
N
N
NH
N
N
N
NH
N
N
N
HN
H
2
N
NH
2
H
2
N
N
N
N
NH
2
N
H
2
N
N
N
N
NH
2
H
NH2
NH2
Dendrimers
Branched polyethylenimine
Figure 11.3
The structures of some commonly used chemical non-viral vectors. DMRIE:
1,2-dimyriotloxypropyl-3-dimethyl-hydroxy ethyl ammonium bromide; DOTAP: dioleoyltrimethy-
lamino propane.
that the neutral lipid helps to facilitate endosomal membrane disruption, enabling better
access of the DNA to the nucleus.
Highly efficient lipid-mediated delivery of DNA and RNA has been attained both
in vitro
and
in vivo
, providing transient and stable transfectants to a wide range of tissues and
organs in many animal species (reviewed in Karmali and Chaudhuri [68]).
In vivo
effi-
ciency is, however, diminished due to interaction of the positively charged lipid/DNA
particles with the negatively charged blood components, such as serum, forming large aggre-
gates that are unable to reach their intended cellular target. By incorporating a hydrophilic
polymer, polyethylene glycol (PEG), which shields the cationic charge, an increase in
stability and transfection efficiency has been achieved [69]. Furthermore, natural target-
ing ligands, such as transferrin [70], folate [71] or various antibodies [72], can be added
to increase tissue specificity. Additional enhancements to lipid-mediated delivery systems
have been explored by adding polylysines [73] and membrane permeabilizing agents [74].
