Provided herein are nucleic acid-cleaving catalytic nucleic acid probes, biosensors and lateral flow biosensor devices and methods and kits of using the probes, biosensors and lateral flow biosensor devices for detecting an analyte present on or generated from a microorganism in a test sample, including Helicobacter pylori and methods for determining whether a subject has a Helicobacter pylori infection.

The present invention relates to the field of diagnostics and, more in particular, to MRI activatable contrast agents and compositions thereof for the detection of nuclease activity, wherein said nuclease activity is caused by microbial infection or by nuclease activity related to cancer, particularly colon cancer or pancreatic cancer. Activatable contrast agents for MRI have been developed, wherein the oligonucleotide is flanked by a paramagnetic and a superparamagnetic agent, and thus providing magnetic quenching. Moreover, the oligonucleotide has regions that confer resistance to mammalian endonucleases and sensitivity to microbial endonucleases. When the activatable contrast agent of the invention is in the presence of microbial nuclease activity or a tumour cell nuclease activity, the oligonucleotide is cleaved, agents are unquenched, and the signal derived from the activated contrast agent is detected by MRI.

The present invention relates to polypeptide fragments comprising an amino-terminal fragment of the PA subunit of a viral RNA-dependent RNA polymerase or variants thereof possessing endonuclease activity, wherein said PA subunit is from a virus belonging to the Orthomyxoviridae family. This invention also relates to (i) crystals of the polypeptide fragments which are suitable for structure determination of said polypeptide fragments using X-ray crystallography and (ii) computational methods using the structural coordinates of said polypeptide to screen for and design compounds that modulate, preferably inhibit the endonucleolytically active site within the polypeptide fragment. In addition, this invention relates to methods identifying compounds that bind to the PA polypeptide fragments possessing endonuclease activity and preferably inhibit said endonucleolytic activity, preferably in a high throughput setting. This invention also relates to compounds and pharmaceutical compositions comprising the identified compounds for the treatment of disease conditions due to viral infections caused by viruses of the Orthomyxoviridae family.

Provided is a method for identifying whether an RNA molecule has a 2′-O-methylation modification on a nucleotide, said method comprising: (1) contacting the RNA molecule with a ribonuclease Rnase R; and (2) detecting whether the RNA molecule is degraded or detecting hydrolysis termination positions after degradation. If the RNA molecule is degraded, this indicates that the RNA molecule does not have a 2′-O-methylation modification on a 3′ terminal nucleotide, and if hydrolysis terminates at a same site on multiple random broken fragments, this indicates that the RNA molecule has a 2′-O-methylation modification on the nucleotide at the position immediately preceding the termination site. Also provided are applications of the method for screening for a disease diagnosis target and confirming whether a subject has a 2′-O-methylation modification-related disease.

Methods of detecting a target nucleic acid sequence analyte are provided in which a crRNA and Cas12 or Cas13 enzyme are contacted to form a non-activated RNP. The non-activated RNP is contacted with a sample containing or suspected of containing the target nucleic acid sequence, and the target nucleic acid sequence and non-activated RNP specifically bind to each other if the target nucleic acid is present in the sample, thereby forming an activated RNP. A reporter nucleic acid is contacted with the activated RNP, and the activated RNP indiscriminately cleaves the reporter nucleic acid, reducing passage of intact, non-cleaved reporter nucleic acid through a nanopore in of a nanopore counting device such that a reduction of resistive pulses is produced which provides a signal representative of presence of the target nucleic acid sequence in the sample.

The present disclosure relates, in some embodiments, to isolated nucleic acids (also referred to as cap guides) and methods of use thereof for RNA mapping. The disclosure is based, in part, on guide RNAs that bind to a position that is at least 7 nucleotides downstream of the first nucleotide of an mRNA molecule.

Disclosed herein are methods for evaluation, selection, optimization, and design of Cas9 molecule/gRNA molecule complexes.

The present invention relates to novel probe compounds of formulae I and II defined herein. The present invention also relates to methods of synthesising these novel probe compounds and to their use in assays and screens for determining the binding of a test molecule to the ATP-binding site of a target protein, such as, for example, the Mismatch Repair (MMR) component proteins PMS2 and MLH1, or for determining the location and/or quantity of such target proteins in a biological sample.

This disclosure relates to DNAzymes and biosensors for detecting pathogenic bacteria, and in particular, for detecting Legionella pneumophila. This disclosure also provides a method for detecting the presence of Legionella pneumophila in a test sample, comprising: a) contacting said test sample with the DNAzyme or biosensor described herein, wherein the DNAzyme comprises a detectable label; b) allowing cleavage of the DNAzyme if a target is present, thereby releasing the detectable label; and c) measuring a detectable signal if the portion of the DNAzyme comprising the detectable label is released, wherein the RNA cleavage activity of the DNAzyme is activated by a target from Legionella pneumophila.

A pharmaceutical composition containing human ribonuclease 1 is disclosed. The molecule according to the invention (or the analogous variants) is suitable for use as a medicament for therapy of renal diseases of various aetiologies. The drug according to the invention causes regeneration of glomerular podocytes. The molecule according to the invention can be further used by analytical determination of blood concentration as a marker of disease progression of renal syndromes and for prognosis and prevention of renal insufficiency as a valuable factor of laboratory medicine.