Disclosed are methods, compositions and kits for contacting a sample containing a biological particle with a catalyst associated with or attached to a support. The biological particle may be cells and/or nuclei. The catalyst may be an enzyme configured to digest an extracellular molecule, such as an extracellular biological molecule, including extracellular nucleic acid molecules. In some examples, the biological particle is an aggregate of cells that is processed to single cells with a nuclease that is attached to a bead support. The bead and nuclease may subsequently be removed from the system. The single cells that result from the method can be used in single cell-based droplet systems for obtaining genome or transcriptome profiles of single cells.

The present invention is concerned with methods for analyzing RNA molecules. The provided methods involve conjugates for RNA cleavage comprising a chemical moiety with RNA cleaving activity and an oligonucleotide. The oligonucleotide is designed based on a target sequence present in an RNA molecule, and the cleavage of the RNA molecule is inter alia carried out at conditions allowing the hybridization of the oligonucleotide to the target 5 sequence. Thereby, the method is easily applicable to RNA molecules of any sequence. The method further involves the analysis of the RNA fragments obtained after cleavage to obtain information on the physical properties of the RNA molecule.

Compositions and methods for enriching DNA from any loci of interest are provided. Endonuclease(s) such as RNA-guided nucleases Cpf1/Cas9 can cut the flanking regions of the gene of interest in, for example genomic DNA, followed by ligation of loop adapters. The loop adapters protect the gene of interest for subsequent digestion with one or more exonucleases. Multiple genes of interest can be digested and ligated with loop adapters at the same time. The undigested target sequence can be further purified by, for example, gel extraction using, for example, a commercial DNA purification kit. The enriched DNA can be used for sequencing.