Agriculture Reference
In-Depth Information
A BRIEF HISTORY
Humans.have.been.using.plants.as.a.natural.factory.of.pharmaceutical.molecules.
for. many. centuries.. Many. secondary. metabolites. of. plants. exhibit. a. diversity. of.
therapeutic.effects.including.anti-inlammatory,.wound-healing,.and.antimicrobial.
properties..These.natural.plant.medicines.were.widely.used.around.the.world.by.
early.civilizations.to.protect.and.maintain.human.and.animal.health..Even.today,.
with.our.highly.sophisticated.pharmaceutical.technologies,.more.than.one-quarter.
of. .prescription. pharmaceutics. are. still. derived. from. plants.
1,2
. These. plant-based.
natural.pharmaceuticals.include.single-molecule.drugs.such.as.the.painkiller.mor-
phine.from.the.opium.poppy.and.botanicals.that.are.a.mixture.of.active.plant.mol-
ecules.acting.synergistically.in.the.treatment.of.speciic.conditions..Traditionally,.
these.plant.molecules.are.extracted.from.either.wild.or.cultivated.species..Large-
scale.production,.however,.is.usually.relying.on.modern.advancement.of.plant.tissue.
culture.since.the.medicinal.plants.are.sometimes.rare.in.nature.or.are.dificult.to.
cultivate..Therefore,.plants.and.plant.tissue.cultures.have.been.serving.as.impor-
tant. bioproduction. systems. for. traditional. pharmaceutical. bulk. substances. for. a.
long. time.. With. the. advancement. of. modern. molecular. biology. and. biotechnol-
ogy,.it.became.possible.to.alter.the.plant.genome.by.inserting.expression.cassettes.
including. the. target. transgene. and. associated. regulatory. genetic. elements.. This.
technological.breakthrough.allowed.the.creation.of.transgenic.plants.that.carry.the.
transgene.and.produce.recombinant.proteins.
3
.The.irst.recombinant.pharmaceuti-
cal.protein.of.plant.origin.was.a.human.growth.hormone.produced.in.transgenic.
tobacco.in.1986.
4
.Three.years.later,.the.success.of.expressing.monoclonal.antibod-
ies.(mAbs).in.transgenic.tobacco.plants.was.published,.demonstrating.the.ability.
of. plant. cells. in. expressing. and. assembling. of. complex. functional. multi-subunit.
proteins.
5
. Our. research. group. directed. by. Dr.. Charles. Arntzen. led. the. effort. in.
plant-made.vaccines.and.published.our.irst.inding.in.1992..We.demonstrated.that.
transgenic. tobacco. could. successfully. produce. hepatitis. B. virus. surface. antigen.
(HBsAg).with.similar.biochemical.properties.and.antigenicity.to.that.produced.in.
human.serum.or.recombinant.yeast.
6
.Soon.after,.research.from.our.group.showed.
that.
E. coli
.heat-labile.enteroxin.(LT-B).derived.from.transgenic.tobacco.or.potato.
had. equivalent. functionality. to.
E. coli
-derived. LT-B. and. was. orally. immuno-
genic.in.mice,.which.provided.the.irst.proof.of.principle.for.plant-derived.edible.
vaccines.
7
.The.successes.of.these.researches.opened.up.a.completely.new.applica-
tion.area.for.plants.as.factories.for.human.and.animal.pharmaceutical.production..
In.the.last.two.decades,.a.broad.range.of.functionally.active.vaccines.and.thera-
peutic. proteins. have. been. produced. in. an. increasingly. diverse. species. of. crops.
with.a.variety.of.different.plant.expression.systems..Recent.improvements.in.plant.
expression. vectors. have.allowed. for. signiicant.strides. in. a.variety. of. new.plant-
based.expression.systems.and.their.broad.application..Meanwhile,.the.importance.
of. the. downstream. processing. for. extraction. and. puriication. of. pharmaceutical.
proteins.from.plant.materials.has.been.realized,.and.increasing.efforts.have.been.
applied.to.address.this.critical.issue..The.public.opinion.and.regulatory.landscape.
have.been.evolving.to.a.more.welcoming.climate.where.scientists.and.regulatory.
agencies.can.work.together.to.develop.regulations.and.guidelines.for.plant-made.
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