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Harvesting specific plant metabolites from hairy root cultures using magnetized nanoparticles

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 2R44AT008312-02
Agency Tracking Number: R44AT008312
Amount: $1,029,017.00
Phase: Phase II
Program: SBIR
Solicitation Topic Code: R
Solicitation Number: PA16-302
Timeline
Solicitation Year: 2016
Award Year: 2017
Award Start Date (Proposal Award Date): 2017-04-01
Award End Date (Contract End Date): 2020-03-31
Small Business Information
KTRDC-UK 1401 UNVERSITY DR
Lexington, KY 40546-0001
United States
DUNS: 196165877
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 JOHN LITTLETON
 (859) 255-6757
 jlittlet@uky.edu
Business Contact
 DAVID GIBBS
Phone: (502) 583-7454
Email: dgibbs@blacksheepllc.com
Research Institution
N/A
Abstract

AbstractPlant cell cultures are becoming a commercially valuable source of pharmaceuticalsparticularly
those that are too complex for economical chemical synthesisFor example Phyton Biotechin Germanyhas
achieved great commercial success by generating taxoids for Paclitaxel production in sterile plant cell
bioreactorsHoweverthe efficiency of these systems is limited by the loss in viability of the slow growing plant
cells associated with conventional extraction proceduresThe objective here is to develop a system that
allows plant cells to be harvested repeatedly for high value pharmaceutical products without losing viabilityPhase I demonstrated that nanoparticles can be functionalized to enter plant cells and bind specific bioactive
flavonoid metabolites before being extrudedand these metabolites recoveredall without loss of plant cell
viabilityPhase II now aims to demonstrate that a similarbut more selectiveapproach can be used to harvest
higher value pharmaceuticals from plant cellsi eproof of applicationThe most valuable types of metabolite
currently produced from plants include isoflavonesalkaloids and monoclonal antibodiesthe latter from
transgenic plantsPhase II aims to show that each of these types of product can be harvested from plant cells
by their selective binding to nanoparticles on which specific oligopeptides have been conjugatedEach product
example is relevant to anti cancer therapeuticsThe first is the phytoestrogenliquiritigeninwhich is a selective
agonist of the estrogen receptorER beta that should reduce risk of breast cancer post menopauseThis
flavanone will be harvested from overproducing mutant cultures of licorice root by selective binding to the
ERbeta ligand binding oligopeptide conjugated to nanoparticlesThe second example is to nanoharvest the
chemotherapeutic vinca alkaloidscurrently extracted from intact plant material by Eli Lillyfrom overproducing
mutant cultures of Catharanthus roseusThese alkaloids will be harvested by affinity to nanoparticles bearing
oligopeptides representing their binding sites on human tubulinThese two examples are natural metabolitesbut the most commercially important application of this technology may be to harvest foreign polypeptidesi ebiologicssuch as antibodiesfrom transgenic plant cellsHere the example will be the harvesting from
transgenic tobacco cell cultures of a monoclonal antibodymAbHdirected against tumor cellsSelective
binding will be achieved using nanoparticles in which an oligopeptide mimicking the antibody binding site on
the antigen has been conjugated to the surfaceIn all of these examples the objective is to show that
nanoparticles can repeatedly remove the desired commercial product without loss of plant cell viabilityThis
will reducedown timeand could also reduceresponse timefor example the urgent requirement for
antibodies or vaccines in an outbreak of diseaseIn additionseparation of product by affinity to an
oligopeptide binding site means that the harvested products will be simultaneously semi purifiedPhase II
should demonstrate proof of application for the nanoparticle harvesting technology as applied to high value
anti cancer pharmaceuticalsThe applicants will then move toward commercialization in partnership with
identified pharmaceutical and biotechnology companies in the US and Europesee Commercialization Plan

* Information listed above is at the time of submission. *

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