efficiency of these commercial products but unfortunately none of them have
succeeded [23]. To date, no gene carrier has been approved for use in vivo despite
the increasing numbers of clinical trials in this direction worldwide, and therefore
research in the field of polycations as non-viral gene delivery vectors is still of
prime importance.
It is to be noted that not only water-soluble polymers can be used to complex
DNA, amphiphilic polymers, which depending on the relative ratio of hydrophilic
to hydrophobic block, can also form various self-assembled structures, from spherical micelles to vesicles (polymersomes). This review will be restricted to micelleforming polymers and will exclude polymersomes, which can both encapsulate (in
their aqueous interior) and complex DNA [24, 25].
Since the early years of DNA complexation with cationic polymers, pioneers
from the field of polyelectrolyte complexes between surfactants and/or polymers
led solid physico-chemical studies on the complexation of DNA with
polymers. But it is only more recently, with the rise of more precise instruments
for physico-chemical characterization and appropriate biochemical and biophysical techniques, that the published studies are allowing a direct link to be
drawn between physico-chemical characteristics (such as size, charge, etc.) of
the DNA/polymer (mostly polycations) complexes, also called polyplexes, and
their in vitro and in vivo properties, thus allowing tremendous progresses in the
quest towards polyplexes for gene therapy and their application beyond research
laboratories.
The Introduction will give a brief description of DNA as a biopolymer
(structure, conformations, topologies), some definitions in the field of polyelectrolytes (weak and strong polyelectrolytes), some generalities about DNA/
polycation complexes (factors influencing the complexation, models describing
the structure of the polyplexes, methods adapted to their characterization), and
a description of the parameters to take into consideration for their use in gene
therapy.
Then in Sect. 2, the interpolyelectrolyte complexes (IPEC) between
polycationic polymers and DNA will be addressed as a function of the chemical
structure of the polymer (most of the DNA being used is plasmid DNA, consisting
of many thousands of base pairs). Water-soluble and amphiphilic polymers will be
discussed and then other properties will be taken into consideration such as the
polyelectrolyte’s nature (strong or weak), the presence of steric stabilizers, etc.
Section 3 will deal with complexes of polyamphoteric polymers with DNA. In both
parts, the working line is the correlation between physico-chemical properties and
efficiency in vitro (transfection potency).
Finally, we will give some perspectives on the field opened by new polymerization techniques, and consequently new types of polymers, and on recent
discoveries about how to interfere with the expression of specific genes with
oligonucleotides.
106
A. Bertin
succeeded [23]. To date, no gene carrier has been approved for use in vivo despite
the increasing numbers of clinical trials in this direction worldwide, and therefore
research in the field of polycations as non-viral gene delivery vectors is still of
prime importance.
It is to be noted that not only water-soluble polymers can be used to complex
DNA, amphiphilic polymers, which depending on the relative ratio of hydrophilic
to hydrophobic block, can also form various self-assembled structures, from spherical micelles to vesicles (polymersomes). This review will be restricted to micelleforming polymers and will exclude polymersomes, which can both encapsulate (in
their aqueous interior) and complex DNA [24, 25].
Since the early years of DNA complexation with cationic polymers, pioneers
from the field of polyelectrolyte complexes between surfactants and/or polymers
led solid physico-chemical studies on the complexation of DNA with
polymers. But it is only more recently, with the rise of more precise instruments
for physico-chemical characterization and appropriate biochemical and biophysical techniques, that the published studies are allowing a direct link to be
drawn between physico-chemical characteristics (such as size, charge, etc.) of
the DNA/polymer (mostly polycations) complexes, also called polyplexes, and
their in vitro and in vivo properties, thus allowing tremendous progresses in the
quest towards polyplexes for gene therapy and their application beyond research
laboratories.
The Introduction will give a brief description of DNA as a biopolymer
(structure, conformations, topologies), some definitions in the field of polyelectrolytes (weak and strong polyelectrolytes), some generalities about DNA/
polycation complexes (factors influencing the complexation, models describing
the structure of the polyplexes, methods adapted to their characterization), and
a description of the parameters to take into consideration for their use in gene
therapy.
Then in Sect. 2, the interpolyelectrolyte complexes (IPEC) between
polycationic polymers and DNA will be addressed as a function of the chemical
structure of the polymer (most of the DNA being used is plasmid DNA, consisting
of many thousands of base pairs). Water-soluble and amphiphilic polymers will be
discussed and then other properties will be taken into consideration such as the
polyelectrolyte’s nature (strong or weak), the presence of steric stabilizers, etc.
Section 3 will deal with complexes of polyamphoteric polymers with DNA. In both
parts, the working line is the correlation between physico-chemical properties and
efficiency in vitro (transfection potency).
Finally, we will give some perspectives on the field opened by new polymerization techniques, and consequently new types of polymers, and on recent
discoveries about how to interfere with the expression of specific genes with
oligonucleotides.
106
A. Bertin