Aptamer Science
Transcript of Aptamer Science
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APTAMER SCIENCE:
Aptamers are synthetic or derived low molecular weight, comparatively less
complex oligomers (carbohydrates, proteins, DNA or RNA) which selectively bind a
specifc molecular target. n other words these are molecules with desired binding
specifcity and targeting molecules designed !or specifc purpose. Also they can betermed as small biochemical sensors.
"ecause o! their selective binding a#nity these are use!ul therapeutic means to
target a particular organ or tissue and internali$ed by cells by primarily receptor
mediated endocytosis.
APTAMERS IN CANCER THERAPY (A case study or an example) A PRTEIN!
RNA CN"#$ATE APTAMER
(re%er:Sc&'AM' E T*o t+ousand n&ne)
An experimental nanoparticle therapeutic called %A&AA'$ero one (developed bycalando pharmaceuticals in asadena, %ali!ornia) illustrates the mani!old
advantages that nanoparticle'aptamer mediated cell targetting can oer to cancer
therapeutics. *his seventy nm particle in addition to having a natural tendency to
accumulate in tumors is also designed to home to one or more receptors commonly
!ound on cancer cells the particles mode o! entry also allows them to evade cellular
pumps that e+ect some drugs. roteins on the sur!ace o! the particles as aptamers
target specifc receptors that occur in high concentrations on the sur!ace o! cancer
cells. nce inside the cells, the particles release si'RNA molecules (an aptamer
which can be synthesi$ed and then selectively screened using -&/ method and
binds specifcally to A*), which are tailored to match a specifc gene o! interst andinhibit the manu!acture o! the gene0s encoded protein which may be essential !or
the cancer cell survival.
STR#CT#RE'*he particle is built with biocompatible materials1 a cyclodextrin
containing polymer (%D) with polyethylene glycol (2) stal3s to which trans!errin
proteins (*!) 4protein aptamer are attached.nside, as many as two thousand siRNA
molecules'the therapeutic aptamers are stored. -i'RNA acts as both an aptamer'
targetting A* producing side inside cancer cells and a molecule that the cell0s
protein synthesi$ing and A*' producing machinery.
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si RN
(.2
I$'NE
Pass&,e Tumor tar-ett&n-!
*umors in contrast to other tissue have abnormal blood vessels that have larger
pores suitable !or entry o! nanoparticle. As a result o! this nanoparticles have a
tendency to accumulate in tumors while minimi$ing eects on other parts o! body.
I$' T.
Act&,e Tumor tar-ett&n-!
*rans!errin receptors on the sur!ace o! cancer cell bind to the trans!errin protein on
the nanoparticle, causing the cell to internali$e the nanoparticle by endocytosis.
%D'cyclodextrin
polymer
2'
*!
orous5lea3yvasculature o!
cancerous tissue
Normalvasculature
*! receptors
*!
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62.*7R Controlled Release o% dru- %rom t+e
loaded NP
nce inside the cell, a chemical sensor within the nano particle responds to the
lowering o! p7 within the endocytic vesicle. *his triggers disassembly o! the
nanoparticle and release o! siRNA molecules that will bloc3 a gene0s instructions!rom being translated into a protein that the cancer cell needs to survive.
I$'#RNuclear targetting o! siRNA
a!ter p7 dependent
disintegration o! the
nanoparticle. "lac3 colored
shape represents nucleus and
uncolored smaller vesicle
being the endocytic
vesicle5endosome.