Abstract: Methods of reducing gene expression, protein production and messenger RNA output in a cell are disclosed. Also disclosed is a method for delivering a selected ribozyme to a target mRNA in a cell. The methods are useful for prophylactic and therapeutic purposes.

Abstract: A method of inhibiting the translation of bacterial mRNA is disclosed. The method comprises overexpressing in a bacterium an mRNA which contains a sequence which is complementary to the anti-downstream box region of the 16S rRNA. RNA and DNA constructs for the overexpression of the mRNA of the invention are disclosed. Further, there are disclosed isolated DNA constructs that direct the prolonged expression of a heterologous gene in a cold-shocked bacterium at reduced temperature. The construct can comprise a promoter region of a cold-shocked inducible gene. The replication vehicle comprising such DNA constructs and a method for overexpressing a heterologous gene in a bacterium transformed with such a replication vehicle are also disclosed.

Abstract: The present invention relates to methods for the identification of nucleic acid sequences encoding members of a multimeric (poly)peptide complex by screening for polyphage particles. Furthermore, the invention relates to products and uses thereof for the identification of nucleic acid sequences in accordance with the present invention.

Abstract: The present invention provides a method of reducing the immunostimulatory effects of certain phosphorothioate oligonucleotides used to treat pathogen-mediated disease states and other medical conditions. Immunostimulatory effects of phosphorothioate oligonucleotides are reduced in accordance with the method of the invention by administering the phosphorothioate oligonucleotide in a therapeutic formulation which includes at least one cyclodextrin to a mammal afflicted with the disease or condition being treated. The immune response of the mammal is also monitored in the method of the invention.

Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of NF-kappa-B p65 subunit. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding NF-kappa-B p65 subunit. Methods of using these compounds for modulation of NF-kappa-B p65 subunit expression and for treatment of diseases associated with expression of NF-kappa-B p65 subunit are provided.

Abstract: A method for in vitro selection, from a library of catalyst molecules, of a catalyst molecule of interest having a relatively more efficient specific catalytic activity of interest, as compared to the rest of the catalyst molecules within said library, and wherein said in vitro selection method is characterised by that it allows multiple catalytic activity turn-overs (i.e. substrate to product catalytic activity turn-overs), by the catalyst molecule of interest, before it is finally collected.

Abstract: The present invention relates to a method for obtaining nucleic acid sequences encoding (poly)peptides which increase the expression yields of periplasmic proteins in functional form upon co-expression of said (poly)peptides and said periplasmic proteins. The invention also provides a method for the identification of said (poly)peptides. Furthermore, the present invention relates to a method for increasing the expression yields of periplasmic proteins in functional form by co-expressing (poly)peptides, for example Skp, FkpA, or a homolog of Skp or FkpA, in bacteria.

Abstract: A side-entry excitation arrangement is provided with a multi-channel analyte-separation device. In various embodiments, a plurality of channels are disposed in an array, with a laser disposed to direct an excitation beam of light along a beam path that crosses the longitudinal axes of the channels, so as to simultaneously irradiate a region of each of the channels. Devices of the invention can be useful, for example, in the separation and analysis of bio-molecules, such as DNA, RNA, etc.

Abstract: The invention provides a method of displaying nascent proteins or peptides as complexes with eukaryotic ribosomes and the mRNA encoding the protein or peptide following transcription and translation in vitro, of further selecting complexes carrying a particular nascent protein or peptide by means of binding to a ligand, antigen or antibody, and of subsequently recovering the genetic information encoding the protein or peptide from the selected ribosome complex by reverse transcription and polymerase chain reaction (RT-PCR). The RT-PCR recovery step is carried out directly on the intact ribosome complex, without prior dissociation to release the mRNA, thus contributing to maximal efficiency and sensitivity. The steps of display, selection and recovery can be repeated in consecutive cycles. The method is exemplified using single-chain antibody constructs as antibody-ribosome-mRNA complexes (ARMs).

Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of Her-2. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding Her-2. Methods of using these compounds for modulation of Her-2 expression and for treatment of diseases associated with expression of Her-2 are provided.

Abstract: The invention provides a method of contrast agent drug candidate selection which involves: (i) obtaining a combinatorial library comprising an admixture of potential contrast agent drug candidates each incorporating a reporter moiety which is detectable in the animate human or non-human animal body (e.g. mammalian, avian or reptilian body), said library comprising a plurality of said reporter moieties which are interdistinguishably detectable in said body; (ii) administering said library to an animate human or non-human animal body; (iii) identifying in vivo one or more of said reporter moieties which has a desired distribution and/or elimination pattern in said body and thereby identifying a member of said library which has said pattern site or a sub-set of said library which contains a member of said library which has said pattern.

Abstract: The present invention relates generally to a method of identifying modulators of biological interactions and agents useful for same. More particularly, the present invention contemplates a method of detecting inhibitors of biological interactions involving proteinaceous and/or nucleic acid molecules and more particularly a method of identifying peptide inhibitors of biological interactions having adverse effects on living cells, tissue or organisms. The present invention provides the means by which a wide range of peptide-based therapeutic, prophylactic and diagnostic reagents may be developed.

Abstract: Compositions, methods, and kits are provided for efficiently generating and screening a library of highly diverse protein complexes for their ability to bind to other proteins or oligonucleotide sequences. In one aspect of the invention, a library of expression vectors is provided for expressing the library of protein complexes. The library comprises a first nucleotide sequence encoding a first polypeptide subunit; and a second nucleotide sequence encoding a second polypeptide subunit. The first and second nucleotide sequences each independently varies within the library of expression vectors. In addition, the first and second polypeptide subunit are expressed as separate proteins which self-assemble to form a protein complex, such as a double-chain antibody fragment (dcFv or Fab) and a fully assembled antibody, in cells into which the library of expression vectors are introduced.

Abstract: A novel encoding system, compositions for use therein and methods for determining the source, location and/or identity of a particular item or component of interest is provided. In particular, the present invention utilizes a collection of one or more sizes of populations of semiconductor nanocrystals having characteristic spectral emissions, to “track” the source or location of an item of interest or to identify a particular item of interest. The semiconductor nanocrystals used in the inventive compositions can be selected to emit a desired wavelength to produce a characteristic spectral emission in narrow spectral widths, and with a symmetric, nearly Gaussian line shape, by changing the composition and size of the semiconductor nanocrystal. Additionally, the intensity of the emission at a particular characteristic wavelength can also be varied, thus enabling the use of binary or higher order encoding schemes.

Abstract: A nucleic acid catalyst comprising at least one L-nucleotide substitution.

Abstract: A method of fabricating an array with multiple sets of neighboring features. In the method, for each of multiple sets of neighboring features, at least one set of drops is deposited from a corresponding same pulse jet dispenser onto a substrate so as to form the array with the sets formed from drops deposited by respective different dispensers. Apparatus and computer program products which can execute a method of the invention, are also provided.

Abstract: A method for making a directed antisense library against a target transcript is described. A cDNA of the target transcript is cloned in an appropriate cloning vector. Next, a plurality of deletion derivatives of the cloned cDNA is prepared such that the deletions serially extend into the cDNA from one end thereof. The resulting deletion library is then treated such that cDNA is removed from the other end of each cDNA insert, thus obtaining a fragment library having fragments of a selected size. A catalytic core is then inserted into each fragment of the fragment library, resulting in the directed antisense library. An illustrative antisense gene in the hammerhead ribozyme catalytic core. Plasmids for making the antisense library, plasmids and methods for making the fragment library, and a method for identifying target sites for antisense-mediated gene inhibition are also described.

Abstract: The present invention provides a method of cloning a protein coding for a membrane protein without the need of using anyantibody or ligand. The method of cloning a membrane protein comprises selecting a protein having a signal sequence, using a DNA coding for the signal sequence and N-terminal sequence of the protein as the reporter gene, and screening for a gene for a protein having a transmembrane domain(s). The present invention is concerned also with the CDNA obtained by using such method, a vector containing the DNA, a transformant as transformed with the vector, and the transcription product of the DNA as produced by the transformant.

Abstract: The present invention relates to a method for generating a library of peptides based on a peptide of a predetermined molecular mass and to a method of determining the amino acid sequence of the peptide from the library. A set of amino acids that can be present in the peptide are defined, and an allowed library of all possible sequences of the amino acids in the set having a total mass equal to the predetermined molecular mass, allowing for water lost in forming peptide bonds and for protonation, is generated. The allowed library may be generated by first generating a set of all combinations of amino acids having a total mass equal to the predetermined molecular mass of the peptide and then calculating all linear permutations of all amino acids in each such combination. Generally, the molecular mass is determined using a mass spectrometer. A theoretical fragmentation spectrum for every amino acid sequence in the allowed set may also be calculated for use in determining the amino acid sequence of the peptide.

Abstract: The present invention provides arrays having associated modified oligonucleotides that selectively bind to DNA or RNA, methods of making such arrays, assays for using such arrays, and the like. In one embodiment, the arrays of the invention exhibit an increased binding affinity with complementary nucleic acids, and in particular with complementary RNA. In another embodiment, the associated nucleic acids of the array of the invention exhibit substantial acid resistance, allowing the arrays to be treated with low pH solutions. In another embodiment, the modified associated nucleic acids of the array of the invention exhibit substantial resistance to nuclease degradation.