The invention relates to methods for purifying and isolating at least one RNA molecule which interacts with an RNA-binding protein (RBP). The invention also provides nucleic acid adaptors and primers for use in such methods.

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.

The present inventions describes a Facile Accelerated Specific Therapeutic (FAST) pipeline to rapidly design, built and test peptide nucleic acid treatments against mammalian or microbial genes of interest. The invention may include a bioinformatics application for facile and accelerated high throughput design of peptide nucleic acids (PNAs) that act as inhibitors of expression of specific targeted genes by binding to their mRNA to block translation, or PNA activators that can activate expression of target genes by binding to the respective promoter regions and recruitment of transcriptional activators. The invention may further involve automated and high throughput parallel synthesis of a PNA inhibitor/activator library for generation of on-site therapeutic molecules, which may reduce storage requirements, and the development of efficient delivery of therapeutic PNAs to host cells to overcome challenges of transport, toxicity, and bioavailability. The invention may further involve the testing of designed and built PNAs in a high throughput manner in a relevant infection, or mammalian cell culture model. The proposed invention may allow identification of important gene targets, and quickly generate translatable therapies that can be tested under host conditions, and most importantly develop a countermeasure platform that can be deployed on-site in the future to generate therapies in short time scales.

Provided herein are modified Archaeal family B polymerases derived from the Archaeal microorganism Thermococcus sp. EP1 that exhibit improved incorporation of nucleotide analogues utilized in DNA sequences.

Disclosed herein, in some embodiments, non-naturally occurring proteins (e.g., non-naturally occurring modified proteins) that may be useful in the treatment of bacterial and viral infections, including SARS-CoV-2 infection, host cells comprising the same, and methods of treating bacterial and viral infections including SARS-CoV-2 infection. Also provided herein are host cells comprising fusion proteins for split intein-based selection of peptides that bind a target protein, methods of using the same, and methods of identifying peptides that bind a target protein.

Provided is a system for multiplexed genome editing or a two or three-way combinatorial CRISPR screening. Also provided is high-throughput screening of disease-alleviating genetic combinations to identify two-way and three-way synergistic drug combinations as potential treatment regimens. Also provided is a lentiviral three-way combinatorial guide RNA expression cassette and combinatorial guide RNA libraries.

Strategies, systems, compositions, and methods for efficient production of knock-in cellular clones without reporter genes. An essential gene is targeted using a knock-in cassette that comprises an exogenous coding sequence for a gene product of interest (or “cargo sequence”) in frame with and downstream (3′) of an exogenous coding sequence or partial coding sequence of the essential gene. Undesired targeting events create a non-functional version of the essential gene, in essence a knock-out, which is “rescued” by correct integration of the knock-in cassette, which restores the essential gene coding region so that a functional gene product is produced and positions the cargo sequence in frame with and downstream of the essential gene coding sequence.

The present disclosure provides materials and methods for cloning antibodies from single cells in pooled sequence libraries by selective PCR. The compositions and methods relate to isolating, cloning, and/or expressing one or more antibody sequences from a single cell from a pool of cells.

The present invention relates to methods for the joint analysis of regulation of gene expression and gene expression in single cells. Provided are methods for obtaining gene expression information for a single nucleus, the methods comprising deriving a DNA library from the genomic DNA in one or more nuclei and deriving an RNA library from the RNA in one or more nuclei, sequencing the molecules in the RNA library and the DNA library, and correlating the RNA library and the DNA library for each of the one or more nuclei.

The scChIA-Drop method is a microfluidics-based dual-indexing strategy for single-cell and single-molecule chromatin interaction analysis.