Abstract: Aspects of the invention relate to the design and synthesis of nucleic acid libraries. Certain embodiments relate to the design and synthesis of nucleic acid libraries that express polypeptides. In some embodiments, the invention provides methods for analyzing polypeptide sequences and identifying those that may confer undesirable properties in vivo (e.g., poor solubility, high immunogenicity, low stability, etc.). In some embodiments, the invention provides methods for synthesizing a library of nucleic acids having predetermined sequences (e.g., a library of nucleic acids that encode polypeptides having related sequences with predetermined sequence variations).

Abstract: Disclosed are methods of manufacturing synthetic DNAs, that is, DNAs made at least in significant part by chemical synthesis of nucleic acid polymers. Also provided are methods for assembling plural DNAs in the same pool by multiplexed assembly of synthetic oligonucleotides. In exemplary embodiments, the methods involve pre-amplification of one or more oligonucleotides using “universal” primers, reduction of the error rate in oligonucleotide and/or nucleic acid products, and sequence optimization and oligonucleotides design. Also provided are low-purity arrays of nucleic acids and methods for assembling nucleic acids using oligonucleotides obtained from low-purity arrays.

Abstract: Certain aspects of the present invention provide methods for increasing the fidelity of multiplex nucleic acid assembly reactions using one or more mismatch binding proteins. Aspects of the invention also provide kits, compositions, devices, and systems for enriching nucleic acid samples for nucleic acids containing correct sequences using clamped forms of one or more mismatch binding proteins.

Abstract: Provided are methods for de novo design of proteins that are non-immunogenic when administered for therapeutic purposes. The methods involve protein design based on combinations of peptide fragments naturally encountered by the immune system.

Abstract: Disclosed are methods of manufacturing synthetic DNAs, that is, DNAs made at least in significant part by chemical synthesis of polynucleotide polymers. Also provided are methods for assembling plural DNAs in the same pool by multiplexed assembly of synthetic oligonucleotides. In exemplary embodiments, the methods involve pre-amplification of one or more oligonucleotides using “universal” primers, reduction of the error rate in oligonucleotide and/or polynucleotide products, and sequence optimization and oligonucleotides design.

Abstract: Provided herein are compositions and methods for metabolic pathway engineering. The methods involve combining two or more cells expressing potential pathway proteins extracellularly in the presence of reactants. Also provided are libraries of cells expressing a plurality of pathway components and/or a plurality of variants of a given pathway component extracellularly.

Abstract: The present invention provides recombination based methods for assembling nucleic acids. In certain aspects the present invention provides hierarchical assembly methods for producing genome sized polynucleotide constructs. The methods may be used for assembling large polynucleotide constructs, for synthesizing synthetic genomes, or for introducing a plurality of nucleotide changes throughout the genome of an organism. In another aspect, the invention provides cells having increased genomic stability. For example, cells comprising alterations in at least a substantial portion of the transposons in the genome are provided.

Abstract: Disclosed are methods of manufacturing synthetic DNAs, that is, DNAs made at least in significant part by chemical synthesis of polynucleotide polymers. Also provided are methods for assembling plural DNAs in the same pool by multiplexed assembly of synthetic oligonucleotides. In exemplary embodiments, the methods involve pre-amplification of one or more oligonucleotides using “universal” primers, reduction of the error rate in oligonucleotide and/or polynucleotide products, and sequence optimization and oligonucleotides design.

Abstract: In certain aspects the present invention provides methods and compositions related to rational protein design.

Abstract: Disclosed are methods for the practice of systems pharmacology, systems toxicology, and systems pathology using patterns, such as images, reflective of the biological state of subjects such as humans or experimental mammals. The patterns are generated from data obtained from one or more samples from one or more subjects by applying certain data treatment techniques, and are reflective of the biochemistry of the subjects. The patterns are used in drug selection and discovery, assessment of toxicity and drug efficacy, segmentation of populations, discovery of disease subtypes, as surrogate end points, in the assessment of therapeutic options, and for diagnosis and prognosis of disease.

Abstract: Disclosed is a family of novel protein constructs, useful as drugs and for other purposes, termed “adzymes,” comprising an address moiety and a catalytic domain. In some types of disclosed adzymes, the address binds with a binding site on or in functional proximity to a targeted biomolecule, e.g., an extracellular targeted biomolecule, and is disposed adjacent the catalytic domain so that its affinity serves to confer a new specificity to the catalytic domain by increasing the effective local concentration of the target in the vicinity of the catalytic domain. The present invention also provides pharmaceutical compositions comprising these adzymes, methods of making adzymes, DNA's encoding adzymes or parts thereof, and methods of using adzymes, such as for treating human subjects suffering from a disease, such as a disease associated with a soluble or membrane bound molecule, e.g., an allergic or inflammatory disease.

Abstract: The present invention provides, among other things, methods for engineering a spatially conserved motifs into a recipient polypeptide or polypeptide complex that does not naturally contain such a motif.

Abstract: Disclosed is a family of novel protein constructs, useful as drugs and for other purposes, termed “adzymes,” comprising an address moiety and a catalytic domain. In some types of disclosed adzymes, the address binds with a binding site on or in functional proximity to a targeted biomolecule, e.g., an extracellular targeted biomolecule, and is disposed adjacent the catalytic domain so that its affinity serves to confer a new specificity to the catalytic domain by increasing the effective local concentration of the target in the vicinity of the catalytic domain. The present invention also provides pharmaceutical compositions comprising these adzymes, methods of making adzymes, DNA's encoding adzymes or parts thereof, and methods of using adzymes, such as for treating human subjects suffering from a disease, such as a disease associated with a soluble or membrane bound molecule, e.g., an allergic or inflammatory disease.

Abstract: Disclosed is a family of novel protein constructs, useful as drugs and for other purposes, termed “adzymes,” comprising an address moiety and a catalytic domain. In some types of disclosed adzymes, the address binds with a binding site on or in functional proximity to a targeted biomolecule, e.g., an extracellular targeted biomolecule, and is disposed adjacent the catalytic domain so that its affinity serves to confer a new specificity to the catalytic domain by increasing the effective local concentration of the target in the vicinity of the catalytic domain. The present invention also provides pharmaceutical compositions comprising these adzymes, methods of making adzymes, DNA's encoding adzymes or parts thereof, and methods of using adzymes, such as for treating human subjects suffering from a disease, such as a disease associated with a soluble or membrane bound molecule, e.g., an allergic or inflammatory disease.

Abstract: A flange and seal assembly is provided with an annular sealing ring and a mounting component. The annular sealing ring is retained as a part of the mounting component. The mounting component has a mounting end with a mounting flange extending outwardly from the mounting end, and an annular seal receiving recess formed in an axial end surface of the mounting end, and a retaining element extending from the mounting end. A portion of the sealing ring is axially retained between the retaining element and the axial end surface of the mounting end.

Abstract: An open ended tubular body member has a continuous defining side wall formed of rigid sheet material of high tensile strength. This body member is arranged to be driven into the end of a wood pole longitudinally with the grain. The side wall is contoured to have a plurality of adjoining wall portions with adjacent ones of the wall portions being disposed angularly relative to each other and each arranged to intersect the growth rings of the wood in a diagonal direction. The device resists radial checking of the pole due to aging of the pole or moisture changes and also reinforces the pole whereby mounting bolts for brackets or cross arms are arranged to have a positive securement to a pole.