A method of characterizing candidate agents including steps of (a) providing a library of candidate agents attached to nucleic acid tags; (b) contacting the library with a solid support to attach the candidate agents to the solid support, whereby an array of candidate agents is formed; (c) contacting the array with a screening agent, wherein one or more candidate agents in the array react with the screening agent; (d) detecting the array to determine that at least one candidate agent in the array reacts with the screening agent; (e) sequencing the nucleic acid tag to determine the tag sequences attached to candidate agents in the array; and (f) identifying the at least one candidate agent in the array that reacts with the screening agent based on the tag sequence that is attached to the at least one candidate agent.

Array-based enzymatic oligonucleotide synthesis creates a large number of polynucleotides using an uncontrolled and template independent polymerase such as terminal deoxynucleotidyl transferase (TdT). Spatial control of reaction conditions on the surface of the array allows creation of polynucleotides with a variety of arbitrary sequences. Spatial control may be implemented by removing protecting groups attached to nucleotides only at a selected location on the array or by other techniques such as location-specific regulation of enzymatic activity. The ratio of polynucleotides with protecting groups to unprotected polynucleotides used during a cycle of synthesis is adjusted to control the length of homopolymers created by the polymerase. Digital information may be encoded in the enzymatically synthesized polynucleotides. An encoding scheme for representing digital information in a nucleotide sequence accounts for homopolymers in the polynucleotides by collapsing homopolymer strings in the sequence data to a single nucleotide or to a shorter homopolymer.

This invention relates to methods for producing nucleic acid encoded compounds and libraries of nucleic acid encoded compounds. A nascent compound that comprises a scaffold connected to a solid support by a linker is covalently attached to one or more chemical building blocks to form a chemical portion attached to the scaffold. Coding oligonucleotides encoding the one or more chemical building blocks are covalently attached to the nascent compound to form a coding nucleic acid portion attached to the scaffold. A cleaving group is attached to the chemical portion, nucleic acid portion, or scaffold of the compound. The linker is then reacted with the cleaving group, such that the linker is cleaved and the compound released from the solid support. Nucleic acid encoded compounds and libraries and methods for their production are provided.

This invention relates to methods for producing nucleic acid encoded compounds and libraries of nucleic acid encoded compounds. A nascent compound that comprises a scaffold connected to a solid support by a linker is covalently attached to one or more chemical building blocks to form a chemical portion attached to the scaffold. Coding oligonucleotides encoding the one or more chemical building blocks are covalently attached to the nascent compound to form a coding nucleic acid portion attached to the scaffold. A cleaving group is attached to the chemical portion, nucleic acid portion, or scaffold of the compound. The linker is then reacted with the cleaving group, such that the linker is cleaved and the compound released from the solid support. Nucleic acid encoded compounds and libraries and methods for their production are provided.

Provided is a large-storage capacity gene mutation library construction method, capable of synthesizing relatively few oligomer sequences, then assembling same to create a large-storage capacity gene mutation library.

Described herein are methods, compositions, and systems derived from uncultivated microorganisms useful for gene editing.

The present invention is directed to a method for the synthesis of a bi-functional complex comprising a molecule part and an identifier oligonucleotide part identifying the molecule part. A part of the synthesis method according to the present invention is preferably conducted in one or more organic solvents when a nascent bi-functional complex comprising an optionally protected tag or oligonucleotide identifier is linked to a solid support, and another part of the synthesis method is preferably conducted under conditions suitable for enzymatic addition of an oligonucleotide tag to a nascent bi-functional complex in solution.

Provided is a method for replicating a mirror nucleic acid, comprising: reacting a mirror nucleic acid template, a mirror nucleic acid primer and mirror dNTPs/rNTPs in the presence of a mirror nucleic acid polymerase, so as to obtain the mirror nucleic acid.

Compositions and methods are provided for forming a single RNA polynucleotide from a plurality of DNA oligonucleotides in a single reaction chamber using combined reagents in a single step reaction. DNA polymerase, RNA polymerase and single stranded (ss) DNA oligonucleotides are combined where each DNA oligonucleotide has one or more sequence modules, wherein one sequence module in the first ss DNA oligonucleotide is complementary to a sequence module at the 3′ end of the second ss DNA oligonucleotide; and wherein a second module on the first ss DNA oligonucleotide is an RNA polymerase promoter sequence; and forming a single RNA polynucleotide, excluding the RNA promoter sequence, derived from the first and second DNA oligonucleotides

Provided herein are methods and compositions relating to G protein-coupled receptor (GPCR) libraries having nucleic acids encoding for a scaffold comprising a GPCR binding domain. Libraries described herein include variegated libraries comprising nucleic acids each encoding for a predetermined variant of at least one predetermined reference nucleic acid sequence. Further described herein are protein libraries generated when the nucleic acid libraries are translated. Further described herein are cell libraries expressing variegated nucleic acid libraries described herein.