Harvesting specific plant metabolites from hairy root cultures using magnetized nanoparticles
使用磁化纳米颗粒从毛状根培养物中收获特定的植物代谢物
基本信息
- 批准号:9343261
- 负责人:
- 金额:$ 53.03万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-06-01 至 2019-03-31
- 项目状态:已结题
- 来源:
- 关键词:AffectAffinityAgonistAgreementAlkaloidsAntibodiesAntibody Binding SitesAntigensArtificial nanoparticlesBindingBinding SitesBioreactorsBiotechnologyCatharanthus roseusCell Culture TechniquesCell SurvivalCellsCharacteristicsChemicalsComplexDevelopmentDisadvantagedDisease OutbreaksEngineeringEquilibriumEstrogen Receptor betaEuropeExcisionExposure toFlavanonesFlavonoidsFluorescenceGermanyHarvestHumanImmobilizationIn VitroIndividualInternationalIsoflavonesLegal patentLicensingLicoriceLigand BindingMalignant NeoplasmsMonoclonal AntibodiesMutationNicotiana tabacumOligopeptidesPaclitaxelPeptidesPharmaceutical PreparationsPharmacologic SubstancePharmacologyPhasePhytoestrogensPlant RootsPlantsPostmenopauseProceduresProductionProteinsQuartzReaction TimeRiskSourceSterilitySurfaceSystemTaxoidsTechnologyTestingTherapeutic EffectTimeTissuesTobaccoTransgenic OrganismsTransgenic PlantsTubulinVaccinesVinca Alkaloidsanti-cancer therapeuticantigen bindingbasecell injurychemical synthesischemotherapycommercializationcrystallinityexperimental studyindexingkartocidmalignant breast neoplasmmutantnanoparticleneoplastic cellpolypeptideprotein aminoacid sequenceradioligandsolvent extractionsuccess
项目摘要
Abstract: Plant cell cultures are becoming a commercially valuable source of pharmaceuticals, particularly
those that are too complex for economical chemical synthesis. For example Phyton Biotech, in Germany, has
achieved great commercial success by generating taxoids for Paclitaxel production in sterile plant cell
bioreactors. However, the efficiency of these systems is limited by the loss in viability of the slow-growing plant
cells associated with conventional extraction procedures. The objective here is to develop a system that
allows plant cells to be harvested repeatedly for high value pharmaceutical products without losing viability.
Phase I demonstrated that nanoparticles can be functionalized to enter plant cells and bind specific bioactive
flavonoid metabolites before being extruded, and these metabolites recovered, all without loss of plant cell
viability. Phase II now aims to demonstrate that a similar, but more selective, approach can be used to harvest
higher value pharmaceuticals from plant cells (i.e. proof of application). The most valuable types of metabolite
currently produced from plants include isoflavones, alkaloids and monoclonal antibodies (the latter from
transgenic plants). Phase 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 conjugated. Each product
example is relevant to anti-cancer therapeutics. The first is the phytoestrogen, liquiritigenin, which is a selective
agonist of the estrogen receptor (ER)beta that should reduce risk of breast cancer post-menopause. This
flavanone will be harvested from overproducing mutant cultures of licorice root by selective binding to the
ERbeta ligand-binding oligopeptide conjugated to nanoparticles. The second example is to nanoharvest the
chemotherapeutic vinca alkaloids (currently extracted from intact plant material by Eli Lilly) from overproducing
mutant cultures of Catharanthus roseus. These alkaloids will be harvested by affinity to nanoparticles bearing
oligopeptides representing their binding sites on human tubulin. These two examples are natural metabolites,
but the most commercially important application of this technology may be to harvest foreign polypeptides, i.e.
“biologics”, such as antibodies, from transgenic plant cells. Here the example will be the harvesting from
transgenic tobacco cell cultures of a monoclonal antibody (mAbH10) directed against tumor cells. Selective
binding will be achieved using nanoparticles in which an oligopeptide mimicking the antibody-binding site on
the antigen has been conjugated to the surface. In all of these examples the objective is to show that
nanoparticles can repeatedly remove the desired commercial product without loss of plant cell viability. This
will reduce “down time” and could also reduce “response time”, for example the urgent requirement for
antibodies or vaccines in an outbreak of disease. In addition, separation of product by affinity to an
oligopeptide binding site means that the harvested products will be simultaneously semi-purified. Phase II
should demonstrate proof of application for the nanoparticle harvesting technology as applied to high value
anti-cancer pharmaceuticals. The applicants will then move toward commercialization in partnership with
identified pharmaceutical and biotechnology companies in the US and Europe (see Commercialization Plan).
摘要:植物细胞培养物正成为具有商业价值的药物来源
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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JOHN M. LITTLETON其他文献
JOHN M. LITTLETON的其他文献
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{{ truncateString('JOHN M. LITTLETON', 18)}}的其他基金
Mimicking synuclein toxicity in plant cells to identify novel neuroprotective leads
模拟植物细胞中的突触核蛋白毒性以鉴定新型神经保护先导化合物
- 批准号:
10267035 - 财政年份:2018
- 资助金额:
$ 53.03万 - 项目类别:
Mimicking synuclein toxicity in plant cells to identify novel neuroprotective leads
模拟植物细胞中的突触核蛋白毒性以鉴定新型神经保护先导化合物
- 批准号:
10078986 - 财政年份:2018
- 资助金额:
$ 53.03万 - 项目类别:
Development of JR-220 (4-Chlorobenzylidenamino-guanidine hydrochloride) as a medication for alcohol dependence
开发 JR-220(4-氯苯亚基氨基胍盐酸盐)作为酒精依赖药物
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Development of JR-220 (4-Chlorobenzylidenamino-guanidine hydrochloride) as a medication for alcohol dependence
开发 JR-220(4-氯苯亚基氨基胍盐酸盐)作为酒精依赖药物
- 批准号:
9397465 - 财政年份:2017
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$ 53.03万 - 项目类别:
Mutant transgenic plant cells as a novel source of drugs
突变转基因植物细胞作为新的药物来源
- 批准号:
9253077 - 财政年份:2016
- 资助金额:
$ 53.03万 - 项目类别:
Mutant transgenic plant cells as a novel source of drugs
突变转基因植物细胞作为新的药物来源
- 批准号:
9356446 - 财政年份:2016
- 资助金额:
$ 53.03万 - 项目类别:
Harvesting specific plant metabolites from hairy root cultures using magnetized n
使用磁化n从毛状根培养物中收获特定的植物代谢物
- 批准号:
8712853 - 财政年份:2014
- 资助金额:
$ 53.03万 - 项目类别:
Novel flavonoids as anti-inflammatory agents in alcoholism
新型黄酮类化合物作为酒精中毒的抗炎剂
- 批准号:
8251289 - 财政年份:2014
- 资助金额:
$ 53.03万 - 项目类别:
Alcohol, the vagus nerve and multi-organ inflammation
酒精、迷走神经和多器官炎症
- 批准号:
8334496 - 财政年份:2011
- 资助金额:
$ 53.03万 - 项目类别:
Alcohol, the vagus nerve and multi-organ inflammation
酒精、迷走神经和多器官炎症
- 批准号:
8064072 - 财政年份:2011
- 资助金额:
$ 53.03万 - 项目类别:
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