microbot drug delivery
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Microbot Drug Delivery. Which model organism? Mark Fang, Stanford iGEM. Microbots: Overview. - PowerPoint PPT PresentationTRANSCRIPT
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Microbot Drug Delivery
Which model organism?
Mark Fang, Stanford iGEM
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Microbots: OverviewMicrobot drug delivery involves attaching drugs to the exterior of microscopic biological chasses, such as bacteria and viruses, so that when the chasses are phagocytosed by their target cells they bring inside with them the drugs.
Choosing the chassis is thus an important design parameter, since the chassis will be responsible for which cells are targetted and how it will travel to those cells.
In order to get the chassis to localize to the desired targets, we will need to make several considerations:
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Selecting a chassisThe chassis that will transport the drug
should be: Highly specific Immune response Genetically well characterized Pathogenically well characterized
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Bactofection vs. VirofectionTwo broad chassis
classes: Bacteria Viruses
SEM micrograph of Escherichia coliVesicular Somatitis Virus
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Highly SpecificAs with all drug delivery methods, the more
specific, the fewerthe side effects.
The chassis can be engineered to be specific: Quorum sensing Hypoxia Inducible controlThe chassis can also be naturally specific: Listeria monocytogenes Vesicular somatitis virus rp34a
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Immune responseThe patient’s immune response can be a hindrance ora mechanism for inducing localization of the chassis.
Macrophage engulfing bacteria. Thechassis will need to avoid beingengulfed by immune cells to preventincidentally compromising the immunesystem.
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Genetically/structurally well characterizedBacteria: many strains have entire
genome sequenced. Ex. E. coli has been used extensively in genetic engineering.
Virus: more difficult to engineer. Virus may also be too small – for example, lambda phages can only hold genomes between 75 and 105% the size of the normal genome.
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Pathogenically well characterizedNon-pathogenic:
The virulence of certain bacteria species can be attenuated through knock out mutants.
The rate and extent of bacterial expansion can also be controlled.
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Advantages vs. DisadvantagesViruses: More difficult to engineer May be too small Can cause undesirable mutations during
integration of viral genome into host genome Can be naturally specificBacteria: Easier to manipulate, virulence shown to be
pliable, some are also naturally localized in body
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Choosing a chassisListeria monocytogenes – with the view of
targeted drug delivery to cancer cells: Has been show to localize to tumor cells
and metastases Has been engineered to exhibit
attenuated virulence Expansion can be controlled Riboswitches naturally extant in certain
Listeria species
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Testing the chassis HeLa cancer cells – can conduct in vitro test
for general invasion of human cancer cells Human glioma cells - to establish possibility
for chassis to invade brain cancer cells. Further tests in animals may show whether the chassis is able to penetrate the blood brain barrier.
For a listing of 60 human cancer cell lines: http://dtp.nci.nih.gov/docs/misc/common_files/cell_list.html