Gene Delivery Using Physical Methods - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 107

Primary endothelial cells are effectively transfected by magnetofection [254,258] .
In addition, magnetofection is effective for in vitro and in vivo delivery of DNA
to target cells like those in the GI tract and blood vessels [254] , and for antisense
ODNs delivery [259] . Other applications include advances in ex vivo tissue engineer-
ing, development of tumor vaccines, localized therapy for cancer, and cardiovascular
therapy [260] . Significant enhancement in reporter gene expression in a short time
has been observed in the ex vivo porcine airway model; this may be attributed to an
increase in contact time with mucociliary cells, thereby reducing their clearance from
the target site [261] . A study carried out using magnetic albumin microspheres with
entrapped doxorubicin in the rat model for tumors resulted in a high level of tumor
remission in animals compared to animals treated with free doxorubicin, placebo
microspheres, or nonlocalized doxorubicin microspheres, which resulted in consid-
erable enlargement in tumor size associated with metastases and subsequent death
[262,263] . The magnetic nanoparticles with doxorubicin are also under clinical trial
[264] . Magnetofection has been widely used for viral and nonviral vectors and also
for the delivery of DNA, nucleic acids, and siRNA [260,265,266] .
In conclusion, magnetofection is an efficient system for gene delivery and has the
potential to bring in vitro and in vivo transgene transfection in the target organ. The
limitations of this delivery system are overcome by the application of proper formu-
lations and novel magnetic field skills.
3.10 Laser Beam Gene Transduction
�aser beam gene transduction (�BGT) is one of the alternative physical methods for
gene delivery, involving the injection of naked DNA with subsequent laser beam irra-
diation. Neodymium-yttrium-aluminium garnet (Nd: YAG) [267] , holmium-YAG
[268] , argon ion [269] , and titanium sapphire [270] are generally used as the laser
source. The intensity or strength of the emitted laser beam is controlled by the pulse
generator, and the emitted laser beam is concentrated at the target site with the aid of
a lens. The mechanism responsible for laser beam gene transduction is the modifica-
tion in the permeability of the target cell due to local thermal changes associated with
laser beam irradiation. This modification changes the osmotic pressure inside the tar-
get cell and its surrounding medium, a key factor that accounts for the efficient trans-
duction of the gene inside the target cell. In addition, laser beam irradiation produces
transient pores (approximately 2 m in diameter [271,272] ) in the target tissues, which
also helps in gene transduction across the target tissue. The pores so produced are not
permanent, as these get restored automatically within a short period of time [271] .
Gene delivery via �BTS is not extensively used due to the high cost and the physi-
cal size of the laser sources required. In the 1980s, various studies were carried out for
in vitro gene delivery using this method [267,271] , and since then, many studies have
been published [268,272-274] . Most recently, Zeira et al. revealed that gene delivery
in muscle by the laser beam gene transduction (�BTS) is more efficient and safe com-
pared to gene delivery by EP in the same muscle under the same conditions. This find-
ing has been confirmed by the histological study of target tissue receiving �BTS and