Provided herein are polypeptides that bind to a transferrin receptor, methods of generating such polypeptides, and methods of using the polypeptides to target a composition to a transferrin receptor-expressing cell.

The invention relates to a method for analysing ribonucleic acid (RNA) interactions comprising: a) cross-linking base-paired nucleotides of at least one RNA molecule and/or at least one pair of RNA molecules using a tagged, reversible cross-linking agent (preferably tagged-psoralen) under ultraviolet irradiation; b) fragmenting the said cross-linked RNA molecule(s); c) using said tag to extract said cross-linked RNA fragment(s); d) ligating the said cross-linked RNA fragment(s) to produce cross-linked ligated RNA chimera(s); e) reversing the cross-linking of the said agent to the said RNA molecule(s); f) preparing a sequence library by sequencing the ligated RNA chimera molecule(s) or pair(s); and g) analysing the sequence library to determine RNA interactions. Also disclosed is a method of studying a subject by analysing RNA interactions and attributing them to a clinical picture, or a drug discovery method by attributing an efficacy score to the drug based upon determined RNA interactions.

The invention relates to a method for analysing ribonucleic acid (RNA) interactions comprising: a) cross-linking base-paired nucleotides of at least one RNA molecule and/or at least one pair of RNA molecules using a tagged, reversible cross-linking agent (preferably tagged-psoralen) under ultraviolet irradiation; b) fragmenting the said cross-linked RNA molecule(s); c) using said tag to extract said cross-linked RNA fragment(s); d) ligating the said cross-linked RNA fragment(s) to produce cross-linked ligated RNA chimera(s); e) reversing the cross-linking of the said agent to the said RNA molecule(s); f) preparing a sequence library by sequencing the ligated RNA chimera molecule(s) or pair(s); and g) analysing the sequence library to determine RNA interactions. Also disclosed is a method of studying a subject by analysing RNA interactions and attributing them to a clinical picture, or a drug discovery method by attributing an efficacy score to the drug based upon determined RNA interactions.

The present disclosure relates to novel macrocyclic compounds and libraries thereof containing heteroaryl moieties that are useful as research tools for drug discovery efforts. The present disclosure also relates to methods of preparing these compounds and libraries and methods of using these libraries, such as in high throughput screening. In particular, these libraries are useful for evaluation of bioactivity at existing and newly identified pharmacologically relevant targets, including G protein-coupled receptors, nuclear receptors, enzymes, ion channels, transporters, transcription factors, protein-protein interactions and nucleic acid-protein interactions. As such, these libraries can be applied to the search for new pharmaceutical agents for the treatment and prevention of a range of medical conditions.

The present disclosure relates to novel macrocyclic compounds and libraries thereof containing heteroaryl moieties that are useful as research tools for drug discovery efforts. The present disclosure also relates to methods of preparing these compounds and libraries and methods of using these libraries, such as in high throughput screening. In particular, these libraries are useful for evaluation of bioactivity at existing and newly identified pharmacologically relevant targets, including G protein-coupled receptors, nuclear receptors, enzymes, ion channels, transporters, transcription factors, protein-protein interactions and nucleic acid-protein interactions. As such, these libraries can be applied to the search for new pharmaceutical agents for the treatment and prevention of a range of medical conditions.

The present invention relates to a method for producing a population of nucleic acids encoding at least one protein comprising at least one immunoglobulin variable domain having a non-human-derived CDR3 amino acid sequence embedded in essentially human framework sequences, as well as to a population of nucleic acids and a population of proteins relates thereto and uses thereof.

The present invention relates to a method for producing a population of nucleic acids encoding at least one protein comprising at least one immunoglobulin variable domain having a non-human-derived CDR3 amino acid sequence embedded in essentially human framework sequences, as well as to a population of nucleic acids and a population of proteins relates thereto and uses thereof.

Disclosed herein are formulations, substrates, and arrays for the synthesis of PNA chains and PNA-DNA chimera on microarrays. In some embodiments, the formulations include a photo-protective compound that shields any PNA monomers, PNA polymers, or PNA-DNA chimera already attached to a microarray from radiation exposure during the synthesis of the PNA or PNA-DNA chains. In some embodiments, substrates and arrays comprise a porous or a planar layer for synthesis and attachment of PNA or DNA monomers, or PNA or PNA-DNA polymers. In some embodiments, disclosed herein are formulations and methods for high efficiency coupling of PNA monomers or PNA polymers to a microarray substrate.

De novo synthesized large libraries of nucleic acids are provided herein with low error rates. Further, devices for the manufacturing of high-quality building blocks, such as oligonucleotides, are described herein. Longer nucleic acids can be synthesized in parallel using microfluidic assemblies. Further, methods herein allow for the fast construction of large libraries of long, high-quality genes. Devices for the manufacturing of large libraries of long and high-quality nucleic acids are further described herein.

Various approaches for generating read-sets from nucleic acid molecules and segments and phasing are disclosed. Nucleic acids are assembled into complexes using binding moieties and exposed nucleic acid ends are tagged with nucleic acid tags. Read-sets can be generated from tagged nucleic acid molecules and segments. Physical linkage relationships between nucleic acid molecules and segments can be examined using the nucleic acid tags. Various approaches to generating read-sets and phasing are presented.