A Novel Technology for Engineering Binders to Membrane Proteins
膜蛋白结合剂工程新技术
基本信息
- 批准号:10040547
- 负责人:
- 金额:$ 22.71万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-08-01 至 2022-07-31
- 项目状态:已结题
- 来源:
- 关键词:Ankyrin RepeatAntibodiesBase SequenceBinding ProteinsBypassCell Surface ReceptorsCell membraneCell surfaceCellsCoinComplementary DNACoupledDNADependenceDrug TargetingEngineeringFosteringG-Protein-Coupled ReceptorsGoalsImmobilizationIn VitroIncubatedIon Channel ProteinLabelLibrariesMagicMammalian CellMembrane ProteinsMessenger RNAMethodsModelingNucleotidesOligonucleotidesPhage DisplayProcessProtein EngineeringProteinsRNARecombinantsRefractoryReportingSamplingSingle-Stranded DNASiteSolidStructureStructure of thyroid parafollicular cellSupporting CellSystemTechnologyTherapeutic Interventionantibody engineeringdesigndruggable targethuman diseasemembernew technologystemsuccesstherapeutic proteintherapeutic targetunnatural amino acids
项目摘要
Antibodies have been coined the ‘magic bullets’ against many human diseases. However, there remains
significant challenges in the engineering of antibodies targeting multi-pass membrane proteins, which
encompass a large number of therapeutic targets such as cell surface receptors and the ion channel proteins.
The difficulty in engineering binders to membrane proteins stems from the limitation of the current in vitro
selection/panning technologies, such as phage display, which require highly purified target protein.
Unfortunately, membrane proteins are often refractory to purification due to their dependence on the cell
membrane for proper folding and activity. Currently, there is no effective in vitro technology for the
discovery/engineering of binders to multi-pass membrane proteins. The overall goal of this study is to develop
a novel technology – SMURF (Simple proxiMity coUpled mRNA display) – for engineering protein binders to
protein targets on the cell surface, thus bypassing the need to purify the target protein. SMURF combines
mRNA display with the proximity-assisted-DNA-assembly phenomenon and, unlike conventional panning in
which all binders to a solid support are enriched, SMURF fosters the enrichment of binders only to a desired
target protein on the cell surface. In Aim 1, we will demonstrate the SMURF principle using oligonucleotides
and optimize the primer sequences. Aim 2 will establish the SMURF enrichment of a model protein in a
mixture of non-target proteins in solution. Finally, in Aim 3, a model protein will be displayed on the
mammalian cell surface and a library of binders will be screened to demonstrate and quantify the whole-cell
SMURF enrichment efficiency. The successful completion of this study will establish a novel technology for
facile discovery/engineering of binders to whole-cell-displayed membrane proteins and should greatly expand
the repertoire of drug targets amenable to therapeutic intervention.
抗体被认为是对抗许多人类疾病的“灵丹妙药”。然而,仍然存在
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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Zhilei Chen其他文献
Zhilei Chen的其他文献
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- 资助金额:
$ 22.71万 - 项目类别:
A Novel Technology for Engineering Binders to Membrane Proteins
膜蛋白结合剂工程新技术
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7708619 - 财政年份:2009
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$ 22.71万 - 项目类别:
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