The purpose of the present invention is to provide a method for identifying antibody CDR3 clusters using high speed in vitro screening a library selected from the group consisting of cDNA library and nucleic acid aptamer library comprising: (i) preparing a positive spherical shaped structure by binding a target molecule to a spherical shaped molecule, wherein the target molecule is immobilized on the positive spherical shaped structure, wherein the positive spherical shaped structure may contain a fluorescent label; (ii) preparing a negative spherical shaped structure, wherein the target molecule is not immobilized on the negative spherical shaped structure, wherein the negative spherical shaped structure may contain a fluorescent label; (iii) forming a positive spherical shaped conjugate or a negative spherical shaped conjugate by binding a target detecting molecule capable of binding to the target molecule to the positive spherical shaped structure or to the negative spherical structure, wherein the target detecting molecule is selected from the library having a size equal to or more than 10.sup.10 or equal to or less than 10.sup.14, wherein the target detecting molecule may contain a fluorescent label; (iv) separating the positive and the negative spherical shaped conjugates using a fluorescence cell sorter; (v) selecting the separated positive and the separated negative spherical shaped conjugates at least 1 time and then eluting the selected conjugates to obtain an eluted sample; (vi) amplifying a nucleic acid in the eluted sample using PCR to obtain PCR products; (vii) separating the PCR products using the fluorescence cell sorter; and (viii) conducting amplicon sequencing for CDR3 cluster analysis to identify the antibody CDR3 clusters.

The invention provides eukaryotic cell-based screening methods to identify an aptamer that specifically binds a ligand, or a ligand that specifically binds an aptamer, using a polynucleotide cassette for the regulation of the expression of a reporter gene where the polynucleotide cassette contains a riboswitch in the context of a 5′ intron-alternative exon-3′ intron. The riboswitch comprises an effector region and an aptamer such that when the aptamer binds a ligand, reporter gene expression occurs.

The present invention relates to a CRISPR-Cas based system for targeting nucleic acid sequences. In part, the invention relates to synthetic guiding components for targeting single-stranded sequences, as well as design principles for constructing such components. Also described herein are methods of employing such components, e.g., to repress or activate a desired target within the subject.

Oligonucleotide constructs are described, each comprising a functional element and a coding element, wherein the functional element comprises a functional sequence, the functional sequence comprising a sequence of nucleotides in which one or more, or each, nucleotide is modified and the coding element comprises a coding sequence, the coding sequence comprising a sequence of nucleotides which do not contain the modifications of the functional sequence, wherein the coding sequence encodes the sequence structure of the functional sequence.

The invention relates to a method for purifying biologically active GLA-domain coagulation proteins, comprising the following steps: a) bringing a sample that contains one or more GLA-domain coagulation proteins and may contain biologically inactive molecules of GLA-domain protein(s), into contact with an affinity support on which nucleic aptamers that bind specifically to at least one biologically active GLA-domain coagulation protein are immobilized, in order to form complexes between (i) said nucleic aptamers and (ii) said GLA-domain coagulation protein(s), b) releasing the GLA-domain coagulation protein(s) from the complexes formed in step a), and c) recovering said biologically active GLA-domain coagulation protein(s) in a purified form.

This invention concerns pathological angiogenesis and cancer, related treatment methods, and related compositions. Also disclosed are related diagnosis kits and methods.

Provided herein are bispecific personalized aptamers that induce the cell death of cancer cells and methods of use thereof.

Efficient sequence specific gene silencing is possible through the use of siRNA technology. Be selecting particular siRNAs by rational design, one can maximize the generation of an effective gene silencing reagent, as well as methods for silencing genes. Methods compositions, and kits generated through rational design of siRNAs are disclosed, including those directed to the nucleotide sequences for AAT.

Efficient sequence specific gene silencing is possible through the use of siRNA technology. Be selecting particular siRNAs by rational design, one can maximize the generation of an effective gene silencing reagent, as well as methods for silencing genes. Methods compositions, and kits generated through rational design of siRNAs are disclosed, including those directed to the nucleotide sequences for F12.

Provided are a system for constructing a genome-wide sgRNA library and a use thereof. The system includes an input module, an sgRNA design module and an sgRNA filtering module. By constructing three modules in the system, optimizing details and processes in the modules, and adopting multiple design criteria and screening principles, the genome-wide sgRNA library is finally constructed. The system and method are concise and efficient, and the obtained library has a high quality and good activity, and is convenient for applications in gene editing researches.