Biomedical Engineering Reference
In-Depth Information
cells that have the ability to present the antigen and to elicit T cell-mediated immu-
nity [178] . In vaccinating, DNA is introduced into tissues like the skin or muscles,
either by gene gun or intramuscular route. Immunization via the intramuscular route
(predominately Th1 response with mostly IgG2a anti-H1 Ab) differs from immuniza-
tion conveyed with a gene gun (predominately Th2 response with mostly IgG1 anti-
H1 Abs) with respect to the type of immune response [179-181] . However, when
used in combination, these two approaches elicit very effective immunization. The
application of the gene gun in genetic vaccination of tissue, such as skin in pigs
[182] , rhesus monkeys [162] , and horses [183] , was found to elicit humoral as well
as cellular immune responses, which prevents the animals from contracting viral,
bacterial, and parasite infection. The gene gun has been used to successfully deliver
plasmid DNA for boosting immunity against influenza virus in mice, and this route
was found to show the greatest efficiency compared to other routes like intramuscu-
lar or intravenous injection [150] .
Gene gun delivery of mRNA in situ is very efficient for transgene expression and
genetic immunization. When mRNA responsible for firefly luciferase, human growth
hormone and human alpha-1 antitrypsin was delivered by gene gun, it boosted anti-
body response in monolayer and suspension cell cultures in rat liver, mouse liver, and
epidermal tissues [184] . DNA can also be transferred to the rat brain by a specialized
type of gene gun that prevents mechanical damage to the brain [185] . A significant
increase in hematocrit value has been found when an EPO-encoding DNA plasmid is
transferred by gene gun [186] . In addition, the gene gun is also applicable to deliver
lipophilic dyes to the brain, which helps in identifying the structure and function of the
neurons [187] . This effectiveness makes gene gun delivery applicable in the treatment
of cancer and also in vaccination for different types of cancer like prostate cancer,
breast cancer, colon cancer, and several types of lymphomas [188] . Gene gun delivery
is widely used in transfecting various cells like NIH 3T3 [148] , primary myotubes
[147] , COS-7 cells, macrophage cell line [189] , chick myotubes [190] , tissue explants
[145] , and mouse liver in situ [190] . Moreover, the gene gun is useful in establishing
protocols for the treatment of AIDS, including delivery of gold particles coated with
mutant HIV Rev M10 gene in vitro to isolated CD4 cells [191] . In addition, the gene
gun approach is useful for transmitting the pro-opiomelanocortin gene for bladder
pain in rat [192] and for gene transfer into the heart [193] . Gene gun has been used
for in vitro transfection of IL-10 , IL-12 , and B7.1 to murine cell lines in which the
tumor formation was found to be decreased in the MCA205 cell line. Gene gun deliv-
ery of IL-12 was useful for treating developed tumors, but not in B7.1 gene gun deliv-
ery. When large amounts of IL-12 were introduced by the gene gun to induce more
efficient outcomes in the cells, the results were not satisfactory [194] . The gene gun
is also useful for delivering cytokine genes, such as GM-CSF, I�-6, TNF-, IFN-
[166] , and tumor-associated antigens, like HPV E7 [195] , CEA [196] , and MART 1
[197] , in vivo for efficient regulation of tumor growth. Thus in conclusion, the gene
gun is a fast, simple, and flexible method, and requires only a small amount of gene
for efficient transcription results with less toxicity profile. �ike the hydrodynamic
delivery system, it also does not require any complicated instruments, but it is a costly
delivery system. The efficacy of the gene gun depends on factors like particles and
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