Synthetic Genomics, Inc.

Leland Stanford Junior University

Eli Lilly and Company

Vertex Pharmaceuticals, Inc.

Massachusetts Institute of Technology

The Uab Research Foundation (the University of Alabama at Birmingham)

John Irvin Glass

J Craig Venter

Clyde A Hutchison

Hamilton O Smith

Carole Lartigue

Xicheng David Sun

Jeffrey S Glenn

Daniel Glenn Gibson

Deqi Guo

Nancy June Snyder

Frantz Victor

Mark Joseph Tebbe

Q May Wang

Jason Eric Lamar

Cristina Garcia-Paredes

Yvonne Yee Mai Yip

Robert Edward Babine

Charles E Merryman

Raymond Samuel Parker, Iii

Ling Jin

Ivan Collado

Tina Marie Myers

Gwynedd A Benders

Sanjay Vashee

Luc J Farmer

Robert B Perni

Lei Young

Ray-Yuan Chuang

Vladimir N Noskov

Shu Hui Chen

Mikkel A Algire

Neil Adam Gershenfeld

Cheryl Heiner

Andreas Mershin

Elizabeth Strychalski

Shu-Hui Chen

Nacyra Assad-Garcia

Nina Alperovich

Elliot Lefkowitz

Jennifer S Glass

Ellson Y Chen

Gail H Cassell

James Pelletier

May Q Wang

Mai Yee Yvonne Yip

Samuel Raymond Parker Iii

Samuel Raymond Iii Parker

Raymond Samuel Iii Parker

Deqi Duo

In exemplary implementations, transplantation of nucleic acids into cells occurs in microfluidic chambers. The nucleic acids may be large nucleic acid molecules with more than 100 kbp. In some cases, the microfluidic chambers have only one orifice that opens to a flow channel. In some cases, flow through a microfluidic chamber temporarily ceases due to closing one or more valves. Transplantation occurs during a period in which the contents of the chambers are shielded from shear forces. Diffusion, centrifugation, suction from a vacuum channel, or dead-end loading may be used to move cells or buffers into the chambers.

Methods and apparatus for transplantation of nucleic acid molecules

A method to assemble any desired nucleic acid molecule by combining cassettes in vitro to form assemblies which are further combined in vivo, or by assembling large numbers of DNA fragments by recombination in a yeast culture to obtain desired DNA molecules of substantial size is described.

Assembly of large nucleic acids

The presently disclosed invention relates to methods of installing a genome isolated from one species (the donor) into suitably prepared cells of a second species (the recipient). Introduction of the donor genetic material into the recipient host cell effectively converts the recipient host cell into a new cell that, as a result of the operation of the donated genetic material, is functionally classified as belonging to the genus and species of the donor genetic material.

Methods of genome installation in a recipient host cell

A method is provided for introducing a genome into a cell or cell-like system. The introduced genome may occur in nature, be manmade with or without automation, or may be a hybrid of naturally occurring and manmade materials. The genome is obtained outside of a cell with minimal damage. Materials such as a proteins, RNAs, polycations, nucleoid condensation proteins, or gene translation systems may accompany the genome. The genome is installed into a naturally occurring cell or into a manmade cell-like system. A cell-like system or synthetic cell resulting from the practice of the provided method may be designed and used to yield gene-expression products, such as desired proteins. By enabling the synthesis of cells or cell-like systems comprising a wide variety of genomes, accompanying materials and membrane types, the provided method makes possible a broader field of experimentation and bioengineering than has been available using prior art methods.

Installation of genomes or partial genomes into cells or cell-like systems

Compositions and methods are disclosed herein for cloning a donor genome in a heterologous host cell. In one embodiment, the donor genome can be further modified within a host cell. Modified or unmodified genomes can be further isolated from the host cell and transferred to a recipient cell. Methods disclosed herein can be used to alter donor genomes from intractable donor cells in more tractable host cells.

Methods for cloning and manipulating genomes

Compositions and methods are disclosed herein for cloning a synthetic or a semi-synthetic donor genome in a heterologous host cell. In one embodiment, the donor genome can be further modified within a host cell. Modified or unmodified genomes can be further isolated from the host cell and transferred to a recipient cell. Methods disclosed herein can be used to alter donor genomes from intractable donor cells in more tractable host cells.

An amphipathic helix at the approximate N-terminus of Hepatitis C virus (HCV) nonstructural proteins mediates the association of these proteins with cytoplasmic membranes in infected cells. This association is essential for replication. Thus, assessing the ability of compounds or protocols to disrupt the association of such helices with cytoplasmic membranes permits identification of compounds and protocols which are useful in the treatment of HCV infection. Also useful in the invention are mimics, or function-disrupting ligands, of an amphipathic helix of the nonstructural proteins described herein and antibodies and fragments thereof immunoreactive with said helix.

Agents for treatment of HCV and methods of use

The present invention relates to peptidomimetic compounds useful as protease inhibitors, particularly as serine protease inhibitors and more particularly as hepatitis C NS3 protease inhibitors; intermediates thereto; their preparation including novel stereoselective processes to intermediates. The invention is also directed to pharmaceutical compositions and to methods for using the compounds for inhibiting HCV protease or treating a patient suffering from an HCV infection or physiological condition related to the infection. Also provided are pharmaceutical combinations comprising, in addition to one or more HCV serine protease inhibitors, one or more interferons exhibiting anti-HCV activity and/or one or more compounds having anti HCV activity and a pharmaceutically acceptable carrier, and methods for treating or preventing a HCV infection in a patient using the compositions. The present invention is also directed to a kit or pharmaceutical pack for treating or preventing HCV infection in a patient.

Peptidomimetic protease inhibitors

The present invention relates to peptidomimetic compounds useful as protease inhibitors, particularly as serine protease inhibitors and more particularly as hepatitis C NS3 protease inhibitors; intermediates thereto; their preparation including novel steroselective processes to intermediates. The invention is also directed to pharmaceutical compositions and to methods for using the compounds for inhibiting HCV protease or treating a patient suffering from an HCV infection or physiological condition related to the infection. Also provided are pharmaceutical combinations comprising, in addition to one or more HCV serine protease inhibitors, one or more interferons exhibiting anti-HCV activity and/or one or more compounds having anti HCV activity and a pharmaceutically acceptable carrier, and methods for treating or preventing a HCV infection in a patient using the compositions. The present invention is also directed to a kit or pharmaceutical pack for treating or preventing HCV infection in a patient.

A method of detecting a nucleic acid sequence in serovar 3 includes the steps of isolating a specimen containing nucleic acid; and analyzing the specimen with an assay such as in situ hybridization, Southern blotting, single strand conformational polymorphism, restriction endonuclease fingerprinting (REF), PCR amplification, 5&prime; nuclease assay (TaqMan PCR), and DNA-chip analysis using the nucleic acid sequences SEQ ID Nos:1-181.

Nucleic acid probes and method for detecting Ureaplasma urealyticum

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Indianapolis, IN, United States of America

John Irvin Glass