221results about "Protein nucleotide libraries" patented technology

The disclosure relates to compositions, methods, and processes for the preparation, use, and / or formulation of adeno-associated virus capsid proteins, wherein the capsid proteins comprise targeting peptide inserts for enhanced tropism to a target tissue.

The present invention relates to methods of detecting region(s) of interest in a gene comprising a polyA tail. The region(s) of interest can include gene(s), region(s), mutation(s), deletion(s), insertion(s), indel(s), and / or translocation(s). The region(s) can be greater than or less than 1 kilobases from the polyA tail. Methods can include forming a library of single cell transcripts comprising the region(s) in close proximity to a cell barcode and a unique molecular identifier (UMI). Methods for distinguishing cells by genotype can include amplifying the transcripts using PCR methods and detecting the cell barcode and UMI using single cell sequencing methods. Transcripts can be enriched using tagged region-specific PCR primers. Cell barcodes can be brought into close proximity to the region(s) by circularizing the transcripts. Sequencing of the transcripts can include using primer binding sites added during PCR amplification and library indexes for multiplexed sequencing.

The present invention provides an hBCMA-binding polypeptide comprising at least one motif that binds to hBCMA, wherein the peptide has the following structure: [N-terminal portion]-[Helix 1]-[Spacer portion]-[Helix 2]-[C-terminal portion], and the hBCMA-binding motif is the portion [Helix 1]-[Spacer portion]-[Helix 2]. The present invention further provides a pharmaceutical composition comprising the hBCMA-binding polypeptide, and the use of the hBCMA-binding polypeptide or the pharmaceutical composition for use as a medicament, particularly for the treatment or prevention of cancer.

This invention relates to a method for designing and utilizing a broad RNA modification library that includes all surrounding sequences of the RNA modification. By introducing multiple types of RNA modifications, this invention enables the construction of RNA modification libraries that encompass all possible combinations of surrounding sequences flanking the modified RNA. Therefore, it differs from existing reported methods for constructing RNA modification libraries. Furthermore, using the RNA modification library of this invention for single-molecule RNA sequencing generates a high-quality reference dataset containing all possible combinatorial motifs. If this dataset is used as training data for deep learning (or machine learning), it overcomes the limitations of existing software that is limited to specific RNA modifications or has low prediction accuracy for other modifications. This allows for the development of novel, more accurate RNA modification detection software and the simultaneous detection of multiple RNA modifications.

The present invention provides systems and methods for cell free RNA sequencing. Targeted sequencing can be performed using a set of gene transcripts that are rare abundance in a population of cell free nucleic acid control samples.

The present invention aims to provide an immunoglobulin-binding protein having an improved chemical stability, especially having an improved alkaline stability, or an immunoglobulin-binding protein capable of allowing antibody elution under mild pH conditions, and an adsorbent on which the protein is immobilized. The object is achieved by improving the alkaline stability or the antibody elution property by including an amino acid sequence which is the same as an amino acid sequence of an immunoglobulin-binding domain of protein L derived from a bacterium belonging to the genus Finegoldia except that the amino acid residue(s) at a particular position(s) of the domain in the amino acid sequence is / are substituted with another particular amino acid residues(s).

The present disclosure provides a recombinant Salmonella strain having a Type III secretion system (T3SS) comprising mutation which enhance protein expression and production. Additionally, methods and kits for using the recombinant Salmonella strain for producing a protein of interest are provided. Additionally, an optimized medium that increases protein expression in a Salmonella strain having a Type III secretion system (T3SS) is provided.

Systems and methods for protein engineering. The systems include a sequence testing subsystem and a machine learning subsystem. The sequence testing subsystem is configured to express proteins and test the expressed proteins for a given property. The machine learning subsystem is configured to model the activities of a set of possible proteins in light of the properties of the tested proteins and provide one or more untested proteins in the set to the sequence testing subsystem for subsequent testing. The system can be run in an iterative fashion and be fully automated. Methods of using the systems are provided.

Provided herein are antigen binding proteins that bind to thyroid stimulating hormone receptor (TSHR) and methods of using the same.

The present invention includes compositions and methods useful for the detection of a mutational change, SNP, translocation, inversion, deletion, change in copy number, or other genetic variation within a sample of cellular genomic DNA or cell-free DNA (cfDNA). In some embodiments, the compositions and methods of the present invention provide an extremely high level of resolution that is particularly useful in detecting copy number variations in a small fraction of the total cfDNA from a biological sample (e.g., blood).

The present invention relates to a method for producing a nucleic acid library, the method comprising (1) a step for providing a first library that is composed of mutants produced by randomly introducing mutations in a nucleotide sequence encoding a protein capable of being bound to a target or a protein intended to be bound to the target by a phage display method, (2) a step for subjecting the first library to biopanning to produce a sublibrary and then acquiring data to be used in a machine learning, and (3) a step for performing the machine learning using the data to acquire a second library from the first library on the basis of the machine learning prediction, in which the data used in the machine learning include the sequences of a mutant mass included in the sublibrary in the target-binding sequence elution procedure stage, the estimated strength of binding to the target, and actually measured values for the binding of one or some of the mutants included in the mutant mass to the target.

The present invention provides a simple and inexpensive system for regulating signal peptide performance by using a synthetically evolved nucleotide sequence. The invention further relates to an expression vector comprising the nucleotide sequence. Additionally, the present invention relates to host cell comprising the expression vector. Furthermore, the present invention relates to a recombinant protein expressed by the host cell as well as a method for expressing the recombinant protein.

The present disclosure provides methods, compositions, and systems for evolving virus-like particles (VLPs) having one or more desired properties such as increased production levels, increased cargo packaging efficiency, and / or increased transduction of particular target cell types of interest. The present disclosure also provides libraries for use in such methods, and methods for producing the libraries. Group specific antigen (gag) proteins comprising nucleocapsid protein variants evolved using the methods described herein are also provided herein. The present disclosure also provides VLPs comprising such gag proteins comprising nucleocapsid protein variants. Polynucleotides, vectors, cells, and kits useful for performing the methods described herein are also provided.

The present invention provides cell vaccine platforms, such as vaccine-immune virus opsonization platforms, for inducing a host immune response, as well as methods for producing and using such cell vaccine platforms. [Solution] Several embodiments provide genetically engineered human cells comprising (a) genomic disruption in at least one human leukocyte antigen (HLA) gene or at least one transcription regulator of an HLA gene, and (b) an exogenous nucleic acid encoding a cell surface protein that binds to a protein expressed on the surface of phagocytic or cytolytic immune cells, or a functional fragment or functional variant of the cell surface protein, wherein the binding results in activation of the phagocytic or cytolytic activity of the immune cells.

Described herein are VHH antibody libraries with heavy chain variable domain framework scaffolds that have complementarity determining regions (CDRs) found in naturally occurring human antibodies, and methods for making such antibody libraries. The antibody libraries do not include members that contain one or more liabilities that affect one or more properties of the members.

The present disclosure relates to methods of producing and screening libraries of disulfide rich proteins, for instance to identify binding peptides specific for a target molecule. In some embodiments, the binding peptides comprise disulfide rich proteins. Also provided herein are methods of producing and screening libraries comprising disulfide-rich proteins and molecular chaperones. The present disclosure also relates to methods of producing or expressing soluble disulfide rich proteins, for instance using a suitable host cell. Also provided herein are compositions comprising soluble disulfide rich proteins.

Use of a compound, microarray chip substrate, microarray chip and use and method thereof. The present application provides use of a compound, or a geometric isomer, tautomer, isotopically labeled, hydrate, solvate or salt thereof in chip surface modification. Also provided is a microarray chip substrate modified by the compound, and a microarray chip comprising the microarray chip substrate. The microarray chip substrate of the present application can greatly improve the surface modification function by surface modification, improve nucleic acid synthesis yield, amplify detection signal, and avoid non-specificity and cross-talk. It has a wide application prospect.

The present invention provides a method for constructing a cyclic compound library that overcomes the limitations of conventional ring-closing methods for cyclic compound libraries, has the advantages of milder ring-closing reaction conditions and high generality, can be used to construct monocyclic and bicyclic compound libraries, and involves few side reactions. [Solution] A cyclic compound library and its construction method are provided, which uses a solid support, a molecule containing a photocleavable group, a linker, a building block, a ring-closing A-terminal molecule, and a ring-closing B-terminal molecule at both ends of the reaction synthesis, and utilizes the decomposition of the solid support under light irradiation to complete ring closure of the amino acid residue structures of the ring-closing A-terminal molecule A and the ring-closing B-terminal molecule B through the action of cyclohydrolase. This method, which uses mild ring closure conditions, is more universal and expands the types of chemical reactions and the diversity of the encoded compound library.

A library preparation device is a chip including (a) a biological sample well, (b) an end repair and elution well, downstream from the biological sample well, (c) an adapter ligation and elution well, downstream from the end repair and elution well, and (d) a final library well downstream from the ligation and elution well. The library preparation device is useful in a method of library preparation on a library preparation device.

Provided are methods comprising expressing in a recombinant cell comprising a Cas gene a recombinant error-prone reverse transcriptase (RT) and a recombinant spacer RNA comprising a target sequence for mutagenesis of a DNA sequence in the Cas gene; making a mutagenized cDNA polynucleotide homologous to the DNA sequence in the recombinant cell; expressing a recombinant recombineering system in the recombinant cell; and recombining the mutagenized cDNA with the homologous DNA sequence of the Cas gene in the recombinant cell. Also provided are recombinant cells comprising recombinant coding sequences for a recombinant Cas protein, recombinant error-prone reverse transcriptase (RT), recombinant spacer RNA comprising the target sequence, and recombinant recombineering system.

A binding molecule for enhancing the activity of FIX and FIXa. Specifically provided is a FIX and / or FIXa nanobody or a mutant library thereof. The binding molecule comprises an anti-FIX and / or FIXa single-domain antibody (VHH), and complementarity determining regions CDRs of the single-domain antibody comprise CDR1, CDR2 and CDR3. The nanobody can promote the enzymatic activity of FIX and / or FIXa.

The application discloses a kind of enzyme reformation mutant library construction methods, comprising: according to the gene length of target enzyme, it is divided into multiple gene fragments, the gene fragment division result is determined by the interaction pair in the same gene fragment, wherein, interaction pair is determined according to the three-dimensional structure information of target enzyme by the spatial distance of amino acid pair;According to the amino acid in target enzyme, it is divided into multiple amino acid groups by at least one physicochemical property;According to any interaction pair in the same gene fragment, the two amino acids in it are selected from each amino acid group, and one amino acid is selected from each amino acid group, and the selected amino acid is combined to replace the interaction pair, generate mutant library, for screening mutant.The present application realizes the synchronous combination mutation of collaborative site and the intelligent dimension reduction of library capacity by the intelligent segmentation and physicochemical property grouping strategy guided by structure, so as to significantly improve the efficiency and success rate of mutant screening.

In one aspect, the present disclosure provides a method for producing various virus-derived construct plasmids from starting plasmids (for example, virus-derived construct plasmids of the present disclosure). In one embodiment, a method for producing virus-derived construct plasmids of the present disclosure includes a step of preparing a set of starting plasmids containing at least of a part of nucleic acid sequences required to construct a virus-derived construct, the set of starting plasmids including a set of corresponding alternative unit nucleic acids, and the set of corresponding alternative unit nucleic acids including at least one set of corresponding alternative unit nucleic acids containing different nucleic acid sequences; a step of treating the set of starting plasmids with a restriction enzyme and preparing a mixed solution containing cleaved alternative unit nucleic acid fragments; a step of ligating the cleaved alternative unit nucleic acid fragments to form an integrated nucleic acid; and a step of bringing the integrated nucleic acid into contact with a transformed organism to form virus-derived construct plasmids.

Methods and compositions are provided to identify oligonucleotides that bind targets of interest. The targets include tissues, cells, circulating biomarkers such as microvesicles, including those derived from various diseases. The oligonucleotides can be used in diagnostic and therapeutic applications.

A property of interest for a biopolymer is predicted using a combined model that includes a foundation model and a task-specific model. The foundation model is trained at least in part using chemical mapping data and generates embeddings from biopolymer sequences. The task-specific model takes an embedding generated by the foundation model for a sequence and generates a prediction of whether the corresponding biopolymer molecule has a target property.

To provide a high-throughput single-nucleus and single-cell library, and to provide a method for manufacturing and using the library.SOLUTION: Provided herein are methods for preparing a sequencing library comprising nucleic acids from a plurality of single cells. In one embodiment, the method includes nuclear or cellular hashing which allows for increased sample throughput and increased doublet detection at high collision rates. In one embodiment, the method includes normalization hashing to assist in the estimation and removal of technical noise in inter-cell variability, increasing sensitivity and specificity.SELECTED DRAWING: None

The present invention features a number of methods for identifying one or more compounds that bind to a biological target. The methods include synthesizing a library of compounds, wherein the compounds contain a functional moiety having one or more diversity positions. The functional moiety of the compounds is operatively linked to an initiator oligonucleotide that identifies the structure of the functional moiety.

Systems and methods for sequencing of cell-free RNAs are provided. Targeted sequencing can be performed using a panel of transcripts that are genes of rare abundance within a population of control samples of cell-free nucleic acids.

The present disclosure relates to compositions and methods for the preparation, use and / or formulation of adeno-associated virus capsid protein variants.