Lipoplexes and Polyplexes: From Gene Delivery to Gene Expression - Nanotechnology for the Delivery of Therapeutic Nucleic Acids - page 2

The most efficient gene delivery systems for foreign gene
transfer to eukaryotic cells are viruses. In viral vectors, the genetic
material is part of the genome of a replicative-defective virus.
Penetration, integration, and transcription in the host cell via the
viral natural pathway lead to foreign gene expression. Although
a variety of viral vectors were developed during the last 25 years
[3, 4] and clinical trials using viral vectors have been accomplished
[5], their use is hampered by limitations such as the size of the
foreign gene to be transferred, the risk of intrinsic viral propagation
and immunogenicity [6, 7].
Therefore, in order to circumvent the drawbacks associated
with viral vectors, a variety of non-viral gene delivery systems have
been developed.
Synthetic gene delivery systems will be, in principle, devoid of
propagation risks, will not induce immune responses, and will not
be limited in the size of the foreign gene to be expressed. However,
their capacity to transfect cells by a process that includes tissue-
specific targeting, cell penetration, transgene integration, and/or
transcription remains to be improved. Synthetic gene delivery
systems are more a complementary option to virus-mediated
gene therapy of human diseases rather than a separate approach.
For example, after a first treatment with a viral vector that might
palliate but not cure a given disease, an immune response might
be induced. The synthetic DNA delivery agent can be useful for a
complementary second-round treatment, instead of using a second
dose of the viral vector, whose efficacy might be compromised by the
immune response switched-on during the first treatment. Synthetic
DNA delivery agents are especially recommended for delivering
DNA to tissues resistant to viral gene transfer [8]. Moreover, various
synergistic systems have been described, exploiting the advantages
of both viral and non-viral gene delivery systems, such as adeno-
lipofection or retro-lipofection in which infection with adeno
virus [9-12] or retrovirus [13-15] is performed in the presence of
cationic lipid vectors in tissues, where classical viral transfection is
poor, resulting in improved transgene expression. Another synergy
between different gene transfer methodologies is exemplified by
the plasmovirus [16]. Plasmoviruses are plasmids capable of
expressing all the viral genes required for generating infectious
particles and packaging a defective genome containing a transgene.
Plasmids transfected using cationic lipids transform the transduced
cells into packaging cells that release infectious replication-defective