Abstract: The present disclosure relates to computer-based methods and systems for identifying genes associated with biosynthetic gene clusters (BGCs), including embedded target genes (ETaGs) that are homologs of potential therapeutic targets, using comparative genomics techniques and machine learning models.

Abstract: The present disclosure relates to computer-implemented methods and systems for identifying biosynthetic gene clusters (BGCs) that encode pathways for the production of secondary metabolites. Secondary metabolites that target genes or gene products that are homologous to, e.g., human genes or gene products may have utility as potential drug compounds.

Abstract: The present disclosure relates to methods and systems for identifying genes associated with biosynthetic gene clusters (BGCs), including embedded target genes (ETaGs) that are homologs of potential therapeutic targets. The methods and systems described herein apply a comparative genomics and manual review or machine-learning model to analyze grid representations such as heat maps, which assess across a plurality of diverse genomes distribution of orthologs (e.g., bidirectional best hits) of a plurality of query genes that are co-localized with an anchor gene (e.g., a core synthase gene) of a BGC in a query genome.

Abstract: The present invention relates to chirally controlled oligonucleotides of select designs, chirally controlled oligonucleotide compositions, and methods of making and using the same. In some embodiments, a provided chirally controlled oligonucleotide composition provides different cleavage patterns of a nucleic acid polymer than a reference oligonucleotide composition. In some embodiments, a provided chirally controlled oligonucleotide composition provides single site cleavage within a complementary sequence of a nucleic acid polymer.

Abstract: The present disclosure provides powerful technologies for the development, production, characterization, and/or use of stapled peptide compositions. Among other things, the present disclosure provides strategies for defining amino acid sequences particularly amenable or useful for stapling, as well as technologies, reagents, and systems for developing, producing, characterizing, and/or using stapled peptides having such amino acid sequences. In some embodiments, the present disclosure provides stapled peptide agents and uses thereof including for treating various conditions, disorders or diseases.

Abstract: Among other things, the present disclosure provides various useful agents. In some embodiments, provided agents can bind to beta-catenin. In some embodiments, the present disclosure provides technologies for modulating beta-catenin functions. In some embodiments, the present disclosure provides technologies for preventing and/or treating conditions, disorders or diseases associated with beta-catenin. In some embodiments, the present disclosure provides designed amino acids and agents which can provide improved properties and/or activities.

Abstract: The present disclosure relates to treatment of a subject comprising administering to the subject a compound of formula (I); or a pharmaceutically acceptable salt thereof.

Abstract: The present invention relates to chirally controlled oligonucleotides, chirally controlled oligonucleotide compositions, and the method of making and using the same. The invention specifically encompasses the identification of the source of certain problems with prior methodologies for preparing chiral oligonucleotides, including problems that prohibit preparation of fully chirally controlled compositions, particularly compositions comprising a plurality of oligonucleotide types. In some embodiments, the present invention provides chirally controlled oligonucleotide compositions. In some embodiments, the present invention provides methods of making chirally controlled oligonucleotides and chirally controlled oligonucleotide compositions.

Abstract: Among other things, the present disclosure provides technologies for efficient and effective identification of ETaGs, for example, from fungi genomes. In some embodiments, provided technologies are particularly useful for identifying mammalian targets of biosynthetic products of fungi. In some embodiments, provided technologies are particularly useful for identifying and/or prioritizing human targets for drug development. In some embodiments, provided technologies are particularly useful for developing modulators for human targets based on biosynthetic products of fungi.

Abstract: The present invention provides a new type of alpha-helix nucleating cross-link (“staple”) formed by olefin metathesis of a proline derivative with an alkenyl side chain and another amino acid derivative with an alkenyl side chain. The proline derivatives as described herein have been found to be strong nucleators of alpha-helix formation. The invention also provides moieties for shielding the free amide N—H's at the N-terminus of an alpha-helix, thereby further stabilizing the helix. The proline derivatives, precursors prior to cross-linking, and the cross-linked peptides are provided as well as methods of using and preparing these compounds and peptides.

Abstract: Among other things, the present disclosure relates to designed oligonucleotides, compositions, and methods thereof. In some embodiments, provided oligonucleotide compositions provide altered splicing of a transcript. In some embodiments, provided oligonucleotide compositions have low toxicity. In some embodiments, provided oligonucleotide compositions provide improved protein binding profiles. In some embodiments, provided oligonucleotide compositions have improved delivery. In some embodiments, provided oligonucleotide compositions have improved uptake. In some embodiments, the present disclosure provides methods for treatment of diseases using provided oligonucleotide compositions.

Abstract: Disclosed herein are methods for identifying novel drug candidates.

Abstract: Among other things, the present disclosure provides technologies for modulating functions of beta-catenin. In some embodiments, the present disclosure provides stapled peptides that interact with beta-catenin. In some embodiments, provided stapled peptides interact with beta-catenin at an Axin-binding site of beta-catenin. In some embodiments, the present disclosure provides compounds, compositions and methods for preventing and/or treating conditions, disorders and diseases that are associated with beta-catenin.

Abstract: In some embodiments, the present disclosure provides stapled peptides and compositions thereof. In some embodiments, provided peptides can bind to and modulate functions of estrogen receptor.

Abstract: Among other things, the present disclosure provides technologies for efficient and effective identification of ETaGs, for example, from fungi genomes. In some embodiments, provided technologies are particularly useful for identifying mammalian targets of biosynthetic products of fungi. In some embodiments, provided technologies are particularly useful for identifying and/or prioritizing human targets for drug development. In some embodiments, provided technologies are particularly useful for developing modulators for human targets based on biosynthetic products of fungi.

Abstract: Disclosed herein are methods for identifying novel drug candidates.

Abstract: The present invention relates to chirally controlled oligonucleotides, chirally controlled oligonucleotide compositions, and the method of making and using the same. The invention specifically encompasses the identification of the source of certain problems with prior methodologies for preparing chiral oligonucleotides, including problems that prohibit preparation of fully chirally controlled compositions, particularly compositions comprising a plurality of oligonucleotide types. In some embodiments, the present invention provides chirally controlled oligonucleotide compositions. In some embodiments, the present invention provides methods of making chirally controlled oligonucleotides and chirally controlled oligonucleotide compositions.

Abstract: The present invention provides peptides comprising a sequence of X-6X-5X-4X-3X-2X-1X1PX3X4PX6X7PGX10X11AX13X14X15X16LX18X19X20X21X22X23LX25X26YLX29X30X31X32 wherein the amino acids X-6, X-5, X-4, X-3, X-2, X-1, X1, X3, X4, X6, X7, X10, X11, X13, X14, X15, X16, X18, X19, X20, X21, X22, X25, X26, X29, X30, X31, and X32 are as defined herein. The present invention further provides pharmaceutical compositions comprising the peptides and methods of using the peptides for treating proliferative diseases such as cancer which are associated with Ras. Also provided are methods of screening a library of peptide dimers using a peptide dimer display technology.

Abstract: The present invention provides stapled polypeptides of the Formulae (I) and (VI): and salts thereof; wherein the groups ; R1a, R1b, R1c, R2a, R3a, R2b, R3b, R4a, R4b, RA, RZ, L1a, L1b, L2, L3, XAA, v, w, p, m, s, n, t, and q are as defined herein. The present invention further provides methods of preparing the inventive stapled polypeptides from unstapled polypeptide precursors. The present invention further provides pharmaceutical compositions comprising a stapled polypeptide of Formula (I) or (VI), and methods of using the stapled peptides. The present invention also provides modifications of the staples post ring closing metathesis.

Abstract: The present disclosure provides proteins, nucleic acids, vectors, and host molecules useful for the production of compounds of interest, and methods for their use.