Agilent Technologies, Inc.

University of California

Harvard College

Jeffrey Robert Sampson

Joel Myerson

Daniel Branton

David W Deamer

Mark Albert Akeson

Daniel E Ryan

Douglas J Dellinger

Nicholas Michael Sampas

Bo U Curry

Hui Wang

Zohar H Yakhini

Peter G Webb

Robert Kaiser

Derek Lee Lindstrom

Anna M Tsalenko

Holly Hogrefe

Robert A Ach

Brian Jon Peter

Zoltan Timar

Farren J Isaacs

Paige Anderson

Jesse Rinehart

Subhadeep Roy

Barney E Saunders

Karl Barber

The present invention relates to libraries of phosphopeptide-encoding oligonucleotides and methods of preparing such libraries. The present invention also relates to methods of detecting, visualizing, or screening for phosphorylation-dependent protein-protein interactions using recombinant phosphopeptides and/or phosphopeptide-encoding oligonucleotides. The present invention also relates to sets or kits of oligonucleotides having regions that encode phosphopeptides.

Phosphopeptide-encoding oligonucleotide libraries and methods for detecting phosphorylation-dependent molecular interactions

The present invention relates to modified guide RNAs and their use in clustered, regularly interspaced, short palindromic repeats (CRISPR)/CRISPR-associated (Cas) systems.

Guide RNA with chemical modifications

The present invention relates to guide RNAs having chemical modifications and their use in CRISPR-Cas systems. The chemically modified guide RNAs have enhanced specificity for target polynucleotide sequences. The present invention also relates to methods of using chemically modified guide RNAs for cleaving or nicking polynucleotides, and for high specificity genome editing.

High specificity genome editing using chemically modified guide RNAs

Methods for making a synthetic nucleic acid which comprise:

Pairing code directed assembly

Provided herein, among other things, is a method for producing a ligation product on a support. In some embodiments, the method may comprise hybridizing a first double-stranded oligonucleotides and a second double-stranded oligonucleotide to a substrate comprising surface-tethered oligonucleotides and ligating the distal ends of the first and second double-stranded oligonucleotides together, thereby producing a first ligation product that is tethered to the support at both ends.

On-array ligation assembly

This disclosure provides a method comprising: a) clamping the top and bottom strands of a double stranded DNA molecule to produce a duplex in which the top and bottom strands are linked; b) denaturing the duplex to produce a denatured product; and c) renaturing the denatured product in the presence of a labeled oligonucleotide that is complementary to a sequence of nucleotides in the double stranded DNA molecule, thereby producing a D-loop-containing product. Kits for performing the method and products made by the method are also provided.

Target enrichment and labeling for multi-kilobase DNA

Provided herein is a method comprising: producing a first complex by annealing: a first nucleic acid comprising, in order, a first unique sequence, a first central sequence and a second unique sequence; and a second nucleic acid comprising, in order, said second unique sequence, a second central sequence and a third unique sequence; wherein the first, second and third unique sequences do not hybridize with each other; subjecting said first complex to multiple rounds of primer extension to extend the first and second nucleic acids using each other as a template, thereby producing a first product molecule that contains, in order, the first unique sequence, the first central sequence, the second unique sequence, the second central sequence and the third unique sequence; and circularizing said first product molecule by intramolecularly ligating the ends of said product molecule together. Kits and compositions relating to the method are also provided.

Systems and methods for analysis of polymers, e.g., polynucleotides, are provided. The systems are capable of analyzing a polymer at a specified rate. One such analysis system includes a structure having a nanopore aperture and a molecular motor, e.g., a polymerase, adjacent the nanopore aperture.

Methods and apparatus for characterizing polynucleotides

A method for providing defined mixtures of nucleic acids is described. In certain embodiments, the method uses oligonucleotide probes attached to a solid support as a sequence-specific affinity agent to isolate and facilitate the amplification of defined nucleic acid fragment mixtures.

Element defined sequence complexity reduction

Embodiments of labeled nucleotide compositions are described. Methods are described in which a sample containing RNA is contacted with an enzyme having an RNA ligation activity in the presence of a labeled nucleotide composition to provide labeled RNA. Methods of performing an array analysis of a labeled RNA sample are also described.

Labeled nucleotide composition

A method for sequencing a nucleic acid is provided. In certain embodiments, the method includes contacting a nucleic acid duplex comprising a nucleic acid template and a primer annealed to the template with a reagent mix under primer extension conditions to produce an extended primer and ATP. The reagent mix may contain an adenosine-2'-deoxynucleoside tetraphosphate moiety and a polymerase. The method further includes detecting the produced ATP. Also provided are adenosine-2&#x2032;-deoxynucleoside tetraphosphate moieties that find use in the subject methods. Also provided are kits containing the adenosine-2&#x2032;-deoxynucleoside tetraphosphate moieties for use in the subject methods.

Direct ATP release sequencing

In particular embodiments in accordance with the present invention, a wax-embedded tissue specimen is digested and the resulting digested tissue specimen is purified to provide a purified RNA fraction. The purified RNA fraction is treated with one or more enzymes to provide a sample containing dephosphorylated RNA; the sample is contacted with an enzyme having an RNA ligation activity in the presence of a labeled substrate to provide labeled RNA. Kits for performing the described methods are described. Methods of performing an array analysis of a labeled RNA sample are also described.

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San Francisco, CA, United States of America

Jeffrey Robert Sampson