A method for measuring an oligonucleotide which is simpler and more sensitive and has excellent specificity and quantitative capability compared to the conventional measurement method is provided. Moreover, a method for measuring an oligonucleotide having excellent specificity which can distinguish the intact target oligonucleotide (unchanged form) and a metabolite thereof and detect the unchanged form only is provided. In a hybridization method using a capture probe and an assist probe, by using a capture probe having a short nucleotide length in a certain range and the assist probe and causing hybridization under a specific positional relationship between the nucleotide-lacking-site in a metabolite of a nucleic acid drug and the capture probe, it becomes possible not only to detect the target oligonucleotide in a sample but also to distinguish from a metabolite of the nucleic acid drug.

A method for measuring an oligonucleotide which is simpler and more sensitive and has excellent specificity and quantitative capability compared to the conventional measurement method is provided. Moreover, a method for measuring an oligonucleotide having excellent specificity which can distinguish the intact target oligonucleotide (unchanged form) and a metabolite thereof and detect the unchanged form only is provided. In a hybridization method using a capture probe and an assist probe, by using a capture probe having a short nucleotide length in a certain range and the assist probe and causing hybridization under a specific positional relationship between the nucleotide-lacking-site in a metabolite of a nucleic acid drug and the capture probe, it becomes possible not only to detect the target oligonucleotide in a sample but also to distinguish from a metabolite of the nucleic acid drug.

The present disclosure relates in some aspects to methods, probes, kits, and compositions for analysis of a target nucleic acid, such as in situ generation of a circular probe for detection of a target nucleic acid in a tissue sample.

The present disclosure relates in some aspects to methods, probes, kits, and compositions for analysis of a target nucleic acid, such as in situ generation of a circular probe for detection of a target nucleic acid in a tissue sample.

Provided herein are novel Class 2 Type II and Type V CRISPR-Cas RNA-guided endonucleases, e.g. Cas9 and Cas12 endonucleases, and systems comprising the same. Provided also are methods of making, and methods of use thereof. Exemplary methods of use include modifying target DNAs and detecting targeting DNAs, useful for therapeutic and diagnostic applications. Some of the diagnostic applications may utilise the collateral nuclease activity of an enzyme bound to a target sequence.

Provided herein are novel Class 2 Type II and Type V CRISPR-Cas RNA-guided endonucleases, e.g. Cas9 and Cas12 endonucleases, and systems comprising the same. Provided also are methods of making, and methods of use thereof. Exemplary methods of use include modifying target DNAs and detecting targeting DNAs, useful for therapeutic and diagnostic applications. Some of the diagnostic applications may utilise the collateral nuclease activity of an enzyme bound to a target sequence.

The present disclosure in some aspects relates to methods and compositions for accurately detecting and quantifying analytes present at high levels, such as highly expressed genes in a sample. In some embodiments, a probe-resolution barcode sequence disclosed herein does not specifically correspond to any particular target analyte(s) but can be used to resolve dense optical signals due to spatially overlapping signals associated with different molecules of a target analyte, thereby enabling resolution of signals in a dense “spot” and accurate counting of spots associated with molecules that are in spatial proximity. Also provided are kits comprising probes for use in such methods.

The present disclosure in some aspects relates to methods and compositions for accurately detecting and quantifying analytes present at high levels, such as highly expressed genes in a sample. In some embodiments, a probe-resolution barcode sequence disclosed herein does not specifically correspond to any particular target analyte(s) but can be used to resolve dense optical signals due to spatially overlapping signals associated with different molecules of a target analyte, thereby enabling resolution of signals in a dense “spot” and accurate counting of spots associated with molecules that are in spatial proximity. Also provided are kits comprising probes for use in such methods.

The present invention relates to a method and a DNA nanostructure for detecting a target structure. In particular, the present invention relates to a DNA nanostructure, which ensures a preferably linear dependence on the number of marker molecules and the measurement signal regardless of the physical arrangement of a plurality of such DNA nanostructures by virtue of the skilled selection of the shape of the DNA nanostructure and the placement of the marker molecules attached to it. The invention additionally relates to the use of said DNA nanostructures and other nanoreporters, preferably in combination with adapters which bind specifically to target molecules, in a method for quantifying a plurality of target molecules, preferably in a simultaneous manner, using a multiplex method.

The present invention relates to a method and a DNA nanostructure for detecting a target structure. In particular, the present invention relates to a DNA nanostructure, which ensures a preferably linear dependence on the number of marker molecules and the measurement signal regardless of the physical arrangement of a plurality of such DNA nanostructures by virtue of the skilled selection of the shape of the DNA nanostructure and the placement of the marker molecules attached to it. The invention additionally relates to the use of said DNA nanostructures and other nanoreporters, preferably in combination with adapters which bind specifically to target molecules, in a method for quantifying a plurality of target molecules, preferably in a simultaneous manner, using a multiplex method.