Biomedical Engineering Reference
In-Depth Information
12.2.1 Viral Vectors
The vectors of retroviruses, lentiviruses, adenoviruses, and adeno-associated
viruses have been widely used for gene transfer. Viral methods using viral
vectors for gene transfer to tumor tissue have proved to be very effective
approaches, which allow the achievement of high transfection efficiency. In
series of studies, fiber-mutant adenovirus vectors were developed and used for
cancer gene therapy and induced significant antitumor activity when cytokines
and/or chemokines were employed as therapeutic genes.
13-17
Furthermore,
viral vectors modified with PEG induced evasion ability against the
neutralizing antibody and the accumulation of vectors in tumor tissue as well
as effective tumor-targeted gene transfer.
13,18
A variety of studies has been
reported to use different viral vector systems to transduce MSCs.
19-22
However, many clinical trials in which viral vectors were used have been
terminated, since the application of these vectors had induced unexpected
adverse effects such as toxicities, immunogenicity, and oncogenicity.
23-25
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12.2.2 Nonviral Vectors
An increasing number of nonviral vectors are being developed for the purpose
of gene delivery. These vectors have several advantages, such as ease of
synthesis, cell/tissue targeting, low immune response, and unrestricted plasmid
size.
10,26
Until now, a variety of nonviral delivery carriers, including calcium
phosphate,
27
liposomes,
28
and niosomes,
29
as well as nanoparticles,
30
have
been under development.
31
More recently, a novel transfection vector,
spermine-pullulan, was synthesized by cationization of pullulan with the
chemical introduction of spermine.
32
We compared its transfection efficiency
on rat MSCs with other vectors, including peptide TAT-modified polyethyl-
enimine (PEI)-b-cyclodextrin (Tat-cyd), PEI-cyclodextrin (Cyd), and
Lipofectamine 2000 (Lipofectamine 2k, Invitrogen) (Figure 12.1). It was
proved that the transfection efficiency of spermine-pullulan was equal to that
of Cyd and was higher than that of Tat-cyd and Lipofectamine 2000,
indicating that spermine-pullulan could be used as an effective nonviral gene
transfection vector.
33
Although nonviral vectors hold promise in delivering
therapeutic genes to MSCs, most current studies on these vectors are still
limited to the in vitro evaluation of their transfection efficiency. As viral
vectors can integrate into the host genome, they could result in a stable and
long-term gene expression in vivo.
34
However, the gene expression by the
nonviral system is transient, so that this system is not suitable to carry out
studies involving cells for the treatment of diseases for which gene expression is
required over long periods of time, as the nonviral vectors have a shorter
expression time for the transgenes and a relatively lower transfection
efficiency. It was reported that nonviral gene carriers can also prepare cells
stably expressed through antibiotic selection.
35
However, this procedure is not
practical, as it takes a long time to be performed and to optimize the
conditions. Therefore, to tackle this issue the controlled release of anticancer
