24 results about "Scaffold protein" patented technology

The present invention relates to proteins suitable for being used as scaffolds to which a peptide of interest is bound, or which are comprised within a conjugate to which an agent of interest is attached. It also relates to said conjugates suitable for the selective delivery of their conjugated agents of interest to specific cell and tissue types, wherein said agent can be a therapeutic agent or an imaging agent. It also relates to nanoparticles comprising such conjugates and the therapeutic uses thereof.

This invention relates to antibody-binding lipid nanoparticles comprising antibodies bound to membrane scaffold proteins, and more specifically, to antibody-binding lipid nanoparticles comprising lipids and antibodies bound to membrane scaffold proteins, which are therefore easy to prepare and have excellent specific targeting capabilities.

The invention discloses a bone targeting exosome polypeptide delivery system based on a biological orthogonal strategy and a preparation method and application thereof, and relates to the technical field of biological medicine and drug delivery. The bone targeting exosome polypeptide delivery system based on the biological orthogonal strategy comprises an engineered exosome as a carrier and an osteogenesis-promoting therapeutic polypeptide, wherein the osteogenesis-promoting therapeutic polypeptide is anchored on the membrane surface of the engineered exosome; a fusion protein is displayed on the membrane surface of the engineered exosome, and the fusion protein is formed by fusing a bone targeting ligand and an industrial exosome transmembrane scaffold protein; the osteogenesis-promoting therapeutic polypeptide is connected with the industrial exosome through the flexible spacer arm, and the membrane surface steric hindrance is reduced through the flexible spacer arm so as to improve the accessibility of the active fragment of the polypeptide; the delivery system provided by the invention can improve the targeted enrichment and treatment efficiency of osteogenesis promoting drugs in bone tissues, and is suitable for intervention of bone metabolism related diseases such as osteoporosis, delayed fracture healing, bone defects and the like.

The application discloses application of SCAMP5 in treatment of autism spectrum disorder. The application research proves that, compared with a CON group, VPA-induced ASD rats have significant neurotransmitter release disorder and synapse signal path abnormality in hippocampus, overexpression of SCAMP5 protein can improve abnormal release of Glu, abnormal expression of scaffold protein Homer1b / c and downstream protein IP3R, and meanwhile, can relieve autism-like behaviors, space working memory and synapse development abnormality of ASD rats. The application provides a new target and a new potential drug for treatment of autism spectrum disorder, and provides a new idea for target treatment of ASD by in-depth exploration of potential path in pathogenesis of autism.

The invention provides a chicken tibia strength character molecular genetic marker, and relates to the technical field of poultry genetic engineering breeding. The molecular genetic marker of the chicken tibia strength character is a 390 site SNP of an intron 5 of a chicken Cas scaffold protein family member 4 gene, the SNP site is located at the 203th site of SEQ ID NO: 1, and the polymorphism of the SNP site is G / A. The genotype of the molecular genetic marker is obtained by carrying out PCR amplification and sequencing on primers F: 5 '-CCGTCATGCCTACAAG-3' and R: 5 '-GGGATGTTTCACGGGAGGA-3'. The molecular genetic marker is applied to chicken tibia intensity character auxiliary selective breeding, and can realize early selection of tibia intensity characters and early elimination of unwanted breeding hens, so that the feeding cost is reduced, and the chicken tibia intensity character breeding progress is accelerated.

The present disclosure provides scaffold proteins that serve as framework regions for different sets of complementarity determining regions (CDRs) from source antibodies, where the source antibodies bind to different epitopes. The scaffold proteins find use in generating antigen binding polypeptides in single chain fragment variable (scFv) antibody format from a variety of antibodies of interest. These antigen binding polypeptides can have one or more advantageous properties as compared to a source antibody, such as, increased affinity, increased stability, increased expression in a cell, increased yield, etc. The sequence of a scaffold protein has a sequence identity of less than 68% to the sequence of the framework regions of the source antibody.

The invention relates to the field of bacterial membrane protein structures. More specifically, the invention relates to lipid nanodiscs compartmentalized by SlyB protein oligomers isolated from the outer membrane of Gram-negative bacteria. More specifically, the invention provides for a SlyB nanodisc structure wherein the SlyB-oligomer forms the membrane scaffold protein belt, which is surrounded by outer saccharolipid moieties anchored to the SlyB proteins, and which encloses a lipid bilayer nanodomain containing one or more phospholipid layers, wherein macromolecules such as (outer) membrane protein molecules may be captured and stabilized. More specifically, methods to produce and isolate chemically defined stable SlyB nanodisc particles are disclosed herein. Finally, the invention relates to the use of said SlyB nanodiscs as a self-adjuvanting vehicle, as part of an immunogenic composition, and provides for novel means for use in eliciting an immune response against macromolecules enclosed in said SlyB nanodiscs, or for use in a vaccine composition.

The invention discloses a candida tropicalis engineering bacterium for producing 1, 2, 4-butantriol as well as a construction method and application of the candida tropicalis engineering bacterium, and belongs to the technical field of microorganisms. According to the recombinant candida tropicalis strain constructed by the invention, scaffold protein ligand-enzyme fusion protein is subjected to integrated expression through metabolic engineering transformation, and a scaffold protein structural domain GBD-SH3-PDZ is overexpressed on the basis of the scaffold protein ligand-enzyme fusion protein; a glucose repression gene MIG1 gene is knocked out; the KdcA mutant is subjected to overexpression, the yield of 1, 2, 4-butantriol can be obviously increased, the shake flask yield of 1, 2, 4-butantriol is increased to 2.1 g / L from 0.6 g / L of the original strain BTO-01, the yield is increased by 3.35 times, and the yield of the strain BTO-14 in a 5L tank reaches 11.18 g / L through amplification culture of a fermentation tank.

The invention discloses yarrowia lipolytica genetically engineered bacteria for producing lutein as well as a construction method and application of the yarrowia lipolytica genetically engineered bacteria. According to the invention, the Cu < 2 + > induced promoter pMT2 is introduced, and the lycopene is differentially regulated on the time scale to carry out epsilon-cyclization reaction and beta-cyclization reaction, so that the content of by-product beta-carotene is greatly reduced; by introducing a cipB scaffold protein strategy, a high-efficiency electron transport protein complex for converting alpha-carotene into xanthophyll is constructed, and the content of an intermediate product alpha-cryptoxanthin is effectively reduced; by introducing a synthetic route of cytochrome P450 monooxygenase cofactor heme, the activity of a key catalytic enzyme is improved, and the yield of xanthophyll is effectively improved. The Yarrowia lipolytica engineering strain can utilize common carbon sources and nitrogen sources, the shake flask yield of xanthophyll can reach 93 mg / L after fermentation culture, and the Yarrowia lipolytica engineering strain is an excellent strain with high xanthophyll yield and has great industrial application prospects.

Systems and polypeptide complexes are provided that combine scaffold protein modules with a variety of effector modules, enabling comprehensive and versatile control at the protein, RNA, and DNA levels. In addition, uses of them in the modulation of gene expression and potential uses in the treatment of disease are provided.

The invention provides a novel reverse aldolase and reductase cascaded Bi-BDO independent synthesis pathway, and relates to the technical field of bioengineering, the pathway constructs a non-natural metabolism module composed of a modified reverse aldolase RA variant, 4-hydroxybutyraldehyde reductase AHR and a coenzyme cyclic regeneration enzyme, the RA variant performs hydrophobic modification on a Lys146 site, and the reverse aldolase and reductase cascaded Bi-BDO is obtained. Aldol condensation of a non-phosphorylated substrate hydroxyacetaldehyde is realized to generate a C4 intermediate, RA and AHR are physically anchored by utilizing an artificially synthesized scaffold protein, toxicity of the intermediate is avoided through a substrate channel effect, the intermediate is instantly reduced into 1, 4-butanediol, engineering bacteria of aldA and gapA genes are knocked out, a precursor is generated by utilizing a xylose way, and the 1, 4-butanediol is obtained. The method has the advantages that the method is simple in operation, the reduction reaction is driven by in-situ regeneration of NADPH by adding formate, finally, the high-purity product is obtained through macroporous adsorption resin enrichment and vacuum rectification, the TCA circulation decarboxylation step is omitted, the carbon conversion rate is close to the theoretical limit, effective decoupling of production and growth is achieved, and the yield and purity of Bi-BDO are remarkably improved.

The present invention relates to one or more target-binding molecules, each comprising a binding domain [S1] and a binding domain [S2] that are each capable of binding to a scaffold protein, a binding domain [R1] that is capable of binding to a first receptor protein, and a binding domain [R2] that is capable of binding to a second receptor protein. The target-binding molecule is capable of inducing receptor signaling of a receptor complex, conditioned upon binding to a scaffold protein.

The invention provides a construction method and an application of recombinant yarrowia lipolytica for synthesizing furithrolin. The recombinant yarrowia lipolytica is obtained by introducing a combination of a coding gene of tenosyl ether synthase, a coding gene of cytochrome P450 oxidase, a coding gene of cytochrome P450 reductase, a coding gene of acetyltransferase, a coding gene of cytochrome b5 and a coding gene of scaffold protein, and knocking out a coding gene of phosphatidic acid phosphatase at the same time. The efficient synthesis of the fuchsin is realized. The construction method of the yarrowia lipolytica for biosynthesis of the eriolarynx element, provided by the invention, is simple to operate, and the constructed recombinant yarrowia lipolytica can efficiently produce the eriolarynx element and has relatively high production and application values.

We provide a therapeutic drug delivery polypeptide that can be used for treatment. [Solution] The present invention relates to a protein suitable for use as a scaffold to which a target peptide binds, or a protein contained within a complex to which a target agent binds. It also relates to a complex suitable for selectively delivering a complex of a target agent to specific types of cells and tissues. It also relates to nanoparticles containing such a complex. In one embodiment, a polypeptide is provided comprising (i) 11 β-chain domains designated A, B, C, D, E, F, G, H, I, J, and K, and (ii) 10 loop regions connecting two consecutive β-chain domains, designated AB, BC, CD, DE, EF, FG, GH, HI, IJ, and JK loops, wherein at least one of the loop regions is a homogeneous loop region variant, and at least one of the β-chain domains is a homogeneous β-chain variant.

The present invention relates to an antibody-bound lipid nanoparticle comprising an antibody conjugated with a membrane scaffold protein, and more specifically relates to an antibody-bound lipid nanoparticle which comprises a lipid, and an antibody conjugated with a membrane scaffold protein, and which can be easily produced and has an excellent specific targeting ability.

The invention discloses an expanded artificial scaffold protein, an artificial fibrosome and a preparation method and application thereof, and belongs to the technical field of enzyme engineering. According to the invention, the scaffold proteins containing different numbers of adhesion modules are designed, and the two scaffold proteins are modularly assembled by using a covalent linkage system, so that the oversized artificial scaffold protein of which the number of adhesion modules can reach 19 is successfully constructed, and the scale of the oversized artificial scaffold protein exceeds that of the known natural scaffold protein. The scaffold protein can efficiently carry various catalytic subunits through specific interaction of an adhesion module and a docking module to form an artificial fibrosome. Experiments show that the artificial cellulosome can efficiently degrade cellulose substrates such as crystalline cellulose and the like especially when the scaffold protein contains an extremely high amount of cohesin. The invention provides a novel efficient enzyme complex tool for efficiently degrading lignocellulose biomass, and has a wide application prospect in the fields of biofuel, bio-based chemical production and the like.

This invention provides the application of ARF6 as a scaffold protein in the preparation of engineered extracellular vesicles, belonging to the field of biomedical technology. The application of ARF6 (SEQ ID NO.1) as a scaffold protein in the preparation of engineered extracellular vesicles (EVs) provided by this invention. This invention uses natural full-length ARF6 as a scaffold protein to prepare engineered EVs, fully leveraging its comprehensive advantages of short gene sequence, high editing and synthesis efficiency, strong loading capacity, and good versatility. It effectively overcomes the technical bottlenecks of existing EV drug delivery systems, such as low loading efficiency and complex construction processes, successfully constructing a highly efficient, universal, and safe protein and peptide drug delivery platform. The technical solution of this invention showed good anti-inflammatory effects in both cellular inflammation models and sepsis mouse models, indicating that this invention has significant clinical application value and industrialization prospects in the fields of drug delivery and disease treatment.

An immuno-nanolipoprotein particle (Immuno-NLP) comprising one or more membrane forming lipids, a scaffold protein and an immune cell transmembrane protein, and methods of using immuno-nanolipoprotein particles to deliver immune cell transmembrane protein to immune cells, and related compositions, methods, and systems.

The present invention provides a nanodisc with a membrane scaffold protein. The nanodisc includes a membrane scaffold protein, a telodendrimer and a lipid. The membrane scaffold protein can be apolipoprotein. The telodendrimer has the general formula PEG-L-D-(R)n, wherein D is a dendritic polymer; L is a bond or a linker linked to the focal point group of the dendritic polymer; each PEG is a poly(ethylene glycol) polymer; each R is and end group of the dendritic polymer, or and end group with a covalently bound hydrophobic group, hydrophilic group, amphiphilic compound, or drug; and subscript n is an integer from 2 to 20. Cell free methods of making the nanodiscs are also provided.

The invention belongs to the field of biological manufacturing, and discloses a self-assembled multienzyme complex for trilobatin synthesis as well as a construction method and application of the self-assembled multienzyme complex. According to the invention, phloretin 4 '-O-glycosyl transferase MtP4' GT and sucrose synthase GmSUS are respectively combined and connected with scaffold protein through flexible peptides according to different strategies, and a plurality of recombinant plasmids capable of simultaneously coding MtP4 'GT genes and GmSUS genes are constructed; and respectively introducing the plurality of recombinant plasmids into an escherichia coli host to obtain a plurality of recombinant bacterium multienzyme complexes. The yield of trilobatin generated through catalytic conversion of phloretin is used as a screening index, and an optimized single plasmid co-expression strain pET25b-SpyTag-Linker-PGT-SpyCatch-Linker-SUS-1 / BL21start (DE3) is obtained through screening and used for synthesis of the trilobatin. Meanwhile, the invention constructs a green solvent reaction system for green production of trilobatin. The self-assembled multienzyme complex and green solvent reaction system constructed by the invention has high efficiency and economical efficiency in the aspect of synthesizing trilobatin by directional catalytic conversion of phloretin, and has potential application value for promoting the development of a green biological manufacturing process.

The invention relates to an engineered exosome for local fat reduction and a preparation method thereof, and belongs to the field of biotechnology and medical beauty. Three fusion proteins, namely an Apelin-first scaffold protein, an NRG4-second scaffold protein and an FLRG-third scaffold protein, are simultaneously displayed on a membrane of the engineered exosome. The preparation method comprises the following steps: constructing a nucleic acid sequence for coding the three fusion proteins, cloning the nucleic acid sequence to an expression vector, introducing the expression vector into a mammal host cell, culturing, and separating and purifying from a cell supernatant to obtain the target exosome. The exosome can be further mixed with locally medicinal or cosmetically acceptable auxiliary materials to prepare local fat-reducing compositions such as gel, cream or essence. Three active proteins with complementary functions are synergistically delivered through a single exosome, glucose and lipid metabolism can be regulated and controlled in a multi-channel mode, muscles are maintained, the composition can act on subcutaneous adipose tissue after being smeared, and the fat reducing effect is achieved.

This invention provides the application of agents that inhibit NNMT binding to FGFR1 in the prevention and treatment of tumors. Through mutation analysis and interactomics analysis, it reveals a previously unknown, non-enzyme-dependent role of NNMT in promoting aerobic glycolysis in breast cancer. It discovers that NNMT binds to FGFR1 and acts as a scaffold protein, promoting phosphorylation of PKM2 and LDHA at Y105 and Y10 sites, respectively. By positioning the FGFR1 binding interface to the 140-154 amino acid region of NNMT, this invention designs a competitive cell-penetrating peptide, NNMT-15, which can disrupt the NNMT-FGFR1 interaction, reduce the phosphorylation levels of PKM2 and LDHA, inhibit glycolysis, and suppress proliferation in NNMT-high-expressing cancer cells and cancer-associated fibroblasts. These findings reveal NNMT as a dual-function metabolic regulator and establish the NNMT-FGFR1 scaffolding effect as a targeted therapeutic axis in glycolysis-dependent tumors.

The present invention relates to proteins suitable for being used as scaffolds to which a peptide of interest is bound, or which are comprised within a conjugate to which an agent of interest is attached. It also relates to said conjugates suitable for the selective delivery of their conjugated agents of interest to specific cell and tissue types, wherein said agent 5 can be a therapeutic agent or an imaging agent. It also relates to nanoparticles comprising such conjugates and the therapeutic uses thereof.