Polynucleotides, such as aptamers, comprising at least first one 5-position modified pyrimidine and at least one second 5-position modified pyrimidine are provided, wherein the first and second 5-position modified pyrimidines are different. Methods of selecting and using such polynucleotides, such as aptamers, are also provided.

The present disclosure provides methods and compositions for genetically modifying lymphocytes, for example T cells and/or NK cells. In some embodiments, the methods include reaction mixtures, and resulting cell formulations, that are created using whole blood, or a component thereof that is not a PBMC, and additionally comprise T cells and recombinant retroviral particles having polynucleotides that encode a CAR. In some embodiments, modified lymphocytes are reintroduced into a subject subcutaneously. In some embodiments, polynucleotides that provide T cells the ability to regulate cell survival and proliferation in response to binding to a CAR, are provided.

Compositions and methods for identifying and using cis-regulatory and decoy sequences are disclosed.

Compositions and methods for identifying and using cis-regulatory and decoy sequences are disclosed.

The present invention provides an aptamer that binds to IL-21, an aptamer that binds to IL-21 and inhibits the binding of IL-21 and a receptor thereof, and an aptamer that binds to IL-21 and contains a nucleotide sequence represented by the formula (1): CGRYKACY wherein R is A or G, Y is C or U, and K is G or U.

The present invention relates to a nucleotide aptamer or a variant thereof, or a functional fragment thereof, the medical or diagnostic use thereof, the related pharmaceutical composition and a method for selecting a nucleotide aptamer which specifically binds to exosomes isolated from target cells. The present invention further relates to a kit and nucleic acid coding for the aptamer.

Provided herein are compositions comprising aptamers that specifically bind monocytes and/or macrophage and methods for their use. These aptamer compositions can be used in methods for isolating and/or enriching monocytes and/or macrophages or depleting cell populations of monocytes and/or macrophages. Further provided are methods of using the aptamers or cell populations generated using them in the methods disclosed herein for therapies and/or drug delivery.

One aspect according to the present disclosure relates to a novel nucleic acid ligand which is a new class of nucleic acid compound, the existence of which was considered impossible in the prior art. The novel nucleic acid ligand has specific binding affinity with respect to at least two different targets having three-dimensional structures, and the binding sites for the at least two targets are formed in or from a single nucleic acid ligand. The novel nucleic acid ligand according the present disclosure can simultaneously solve several problems of existing aptamers that the prior art could not solve. One aspect according to the present disclosure relates to a novel screening method for identifying the above-mentioned novel nucleic acid ligand. The novel screening method uses a step for sequentially contacting at least two different targets having three-dimensional structures to screen a novel nucleic acid ligand that was previously thought impossible.

Provided is a design method for dividing primer pairs into reaction containers, the design method showing an optimum division example. The design method for dividing primer pairs into reaction containers has a design step of, for a plurality of target nucleic acids, designing a plurality of primer pairs each composed of two types of primers, an evaluation step of evaluating non-specific amplification inducibility between the primer pairs, and an assignment step of performing an assignment to the reaction containers, based on the non-specific amplification inducibility, such that primer pairs having the non-specific amplification inducibility are not present in the same reaction container. The assignment step has a graph generation step of generating a graph having the primer pairs as vertices and non-specific amplification inducibility as an edge or a data structure equivalent to the graph, a coloring step of applying a solution to a graph coloring problem or the like to the graph to perform coloring such that the vertices adjacent to each other have different colors, and an association step of associating the plurality of colors with the reaction containers to associate the primer pair with the reaction containers of the corresponding colors.

Methods of detecting and quantifying target molecules, such as proteins, in a biological sample are provided. The disclosed methods include capturing target molecules with aptamers, replacing the aptamers with aptamer identification sequences, and then sequencing the aptamer identification sequences using next-generation sequencing techniques.