Biomedical Engineering Reference
In-Depth Information
expression.in.the.host's.tissue..In.addition,.conserved.epitopes.of.antigens.can.be.incorpo-
rated.to.increase.the.broadness.of.immune.responses..For.example,.Inovio.has.employed.
SynCon™.technology,.which.integrates.multiple.antigen.sequences.to.formulate.a.consen-
sus.sequence,.and.increased.the.coverage.or.recognition.of.a.greater.number.of.antigenic.
variations..Consequently,.the.SynCon
TM
-based.inluenza.vaccines.induce.antibodies.that.
provide. cross-clade. protection. in. a. variety. of. animals.
48
. An. obvious. beneit. from. these.
advances.is.the.potential.to.develop.pandemic.vaccines.more.rapidly,.as.DNA.plasmids.are.
safe.and.easy.to.produce.in.large.scales..This.opens.up.options.not.previously.available.to.
many.government.and.health.agencies,.especially.during.this.era.of.increased.bioterror-
ism.threats.
14.5 WhereDoWeGofromHere?
14.5.1 Improvements in the Electroporation Process
A.critical.element.in.eficient.electroporation.of.DNA.into.tissues.is.the.design.of.the.appli-
cators. and. electrodes.. The. applicator. consists. of. an. applicator. with. an. attached. power.
cord. with. the. electrodes. inserted. into. the. applicator. that. also. serves. as. the. DNA. injec-
tion. device.
49
. The. injection/electroporation. combination. may. be. controlled. by. noninte-
grated. or. integrated. injection. systems.. The. nonintegrated. system. has. two. distinct. and.
separate.steps:.the.DNA.is.irst.injected,.and.then.the.needle-electrode.arrays.are.inserted.
in.the.DNA-injected.area.to.deliver.the.electric.pulses..Conversely,.the.integrated.injection.
system. combines. the. injection. and. electroporation,. although. two. distinct. steps. are. still.
required.to.deliver.both.the.DNA.and.the.electric.pulse..The.advantage.of.the.latter.is.that.
both.the.DNA.and.the.electrodes.are.aligned,.reducing.inconsistencies.from.injection.to.
injection.and.misalignment..However,.the.design.of.the.needle,.applicators,.and.electrodes.
will.require.constant.evolution.with.consideration.of.several.factors,.including.ease.of.use,.
patient.tolerability,.and.optimization.of.immune.responses.
While.the.current.generation.of.applicators.has.been.suficient.for.use.in.animal.experi-
ments.and.other.small.preclinical.and.clinical.studies,.improvements.in.the.equipment's.
ease.of.operation.may.be.needed.to.vaccinate.a.large.number.of.patients.in.clinical.studies..
A.movement.to.a.fully.integrated.system.has.reduced.some.of.the.issues.with.usage,.and.
the.trend.is.toward.increased.automation.and.miniaturization.
14.5.2 Increasing Patient Tolerability of Electroporation
An.important.criterion.with.electroporation.modalities.is.patient.acceptability.and.toler-
ability..Insertion.of.the.needle-electrodes.into.muscle.plays.a.role.in.triggering.pain,.and.
this.depends.on.myriad.factors,.including.needle.thickness.and.penetration..In.addition.
to.the.needle-electrode.itself,.the.strength.of.the.electrical.voltage.also.contributes.to.the.
pain.. Pain. increases. with. greater. contact. area. and. higher. electrical. ield. intensity;. thus,.
deeper.injection.of.the.needle-electrode.invariably.causes.more.pain.
One. method. to. reduce. the. pain. would. be. to. make. the. process. less. invasive. by. hav-
ing.smaller.needle-electrodes,.reduced.tissue.penetration,.and.fewer.electric.pulses,.while.
maintaining. transfection. eficiency.. One. example. of. such. a. system. is. the. CELLECTRA
®
.
(Inovio. Pharmaceuticals)-ID. device. (Figure 14.4).. Such. optimizations. have. been. made.
with. a. number. of. applicators,. although. the. route. of. vaccine. delivery. may. limit. several.
