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.

Efficient sequence specific gene silencing is possible through the use of siRNA technology. By 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 nucleotide sequences for TTR.

Methods and systems are provided herein for selecting an affinity reagent which binds a desired peptide epitope in a plurality of sequence contexts. The method relies on obtaining a peptide library, each peptide having the sequence αXβ, wherein X is the desired peptide epitope, wherein each of α and β comprise an amino acid, using the peptide library to select an affinity reagent.

Methods and systems are provided herein for selecting an affinity reagent which binds a desired peptide epitope in a plurality of sequence contexts. The method relies on obtaining a peptide library, each peptide having the sequence αXβ, wherein X is the desired peptide epitope, wherein each of α and β comprise an amino acid, using the peptide library to select an affinity reagent.

The present invention provides methods and compositions for performing ordered multi-step syntheses involving modified nucleic acids by nucleic acid-mediated chemistry. This approach is useful for generating sequence-defined highly functionalized nucleic acid polymers. The invention also provides modified nucleic acid polymers that bind to proteins of interest (e.g., PCSK9 and IL-6), which are implicated in human disease.

The present invention provides a novel nucleoside derivative or a salt thereof, a polynucleotide synthesis reagent, a method for producing a polynucleotide, a polynucleotide, and a method for producing a binding nucleic acid molecule. The nucleoside derivative or a salt thereof of the present invention is represented by the following chemical formula (1). ##STR00001## In the chemical formula (1), Su is an atomic group having a sugar skeleton at a nucleoside residue or an atomic group having a sugar phosphate skeleton at a nucleotide residue, and may or may not have a protecting group, L.sup.1 and L.sup.2 are each independently a straight-chain or branched, saturated or unsaturated hydrocarbon group having 2 to 10 carbon atoms, X.sup.1 is an imino group (—NR.sup.1—), an ether group (—O—), or a thioether group (—S—), and R.sup.1 is a hydrogen atom or a straight-chain or branched, saturated or unsaturated hydrocarbon group having 2 to 10 carbon atoms.

Monocyte-specific nucleic acid aptamers and lipid nanoparticles comprising such for use in drug delivery. Also disclosed herein are use of the aptamer-based lipid nanoparticle drug delivery system for treating heart injury.

The invention relates to a method of reacting one or more L-nucleotides with a first L-nucleic acid in the presence of a D-enzyme that adds the one or more L-nucleotides to the 3′ end of the first L-nucleic acid.

Provided is an anti-CRISPR protein (AcrVIA1), which acts as an inhibitor of the nuclease of Cas13. Cas13 recognizes complementary viral transcripts to trigger the degradation of both host and viral RNA during the type VI CRISPR-Cas antiviral response. AcrVIA1 is provided as an isolated or recombinantly expressed protein comprising the sequence of SEQ ID NO:1, or derivatives thereof, expression vectors that encode the same sequence, and methods of making and using proteins that comprise the same sequence, or derivatives thereof, for inhibiting the function of Cas13 and/or protein complexes and/or ribonucleoprotein complexes that comprise Cas13. The disclosure further includes use of the described inhibitor protein in improved diagnostic assays that include Cas13. Inclusion of the inhibitor is expected to preclude a requirement to reverse transcribe and/or create cDNA amplifications of the particular RNA that is the subject of the analysis.