The Scripps Research Institute

The Dow Chemical Company

Synthorx, Inc.

Process Bonding, Inc.

Achaogen, Inc.

Findlay Industries, Inc.

U.S. Government Nih Division of Extramural Inventions and Technology Resources (deitr)

Floyd E. Romesberg

Mach A. Debenedictis

Floyd E Romesberg

Yorke Zhang

Denis A Malyshev

Aaron W Feldman

Vivian T Dien

Thomas Lavergne

Lingjun Li

Zhengtao Li

Jerod Ptacin

Carolina E Caffaro

David M Steinke

Craig W Potter

Hans Aerni

Emil C Fischer

Michael P Ledbetter

Rebekah J Karadeema

Nathaniel E David

Peter Andrew Smith

Tucker Curran Roberts

Martin K Hitchcock

Brian M Lamb

Ryan Cirz

William J Young

J Daniel Asbury

Frank V Goff

Lyle W Colburn

Anne Xiaozhou Zhou

Mach A Debenedictis

Disclosed herein are methods, compositions and kits for the synthesis of proteins which comprises unnatural amino acids that utilize a mutant tRNA.

Incorporation of unnatural nucleotides and methods thereof

Provided herein are analogs of unnatural nucleotides bearing predominantly hydrophobic nucleobase analogs that form unnatural base pairs during DNA polymerase-mediated replication of DNA or RNA polymerase-mediated transcription of RNA. In this manner, the unnatural nucleobases can be introduced in a site-specific way into oligonucleotides (single or double stranded DNA or RNA), where they can provide for site-specific cleavage, or can provide a reactive linker than can undergo functionalization with a cargo-bearing reagent by means of reaction with a primary amino group or by means of click chemistry with an alkyne group of the unnatural nucleobase linker.

Method for the site-specific enzymatic labelling of nucleic acids in vitro by incorporation of unnatural nucleotides

Disclosed herein are methods, cells, engineered microorganisms, and kits for increasing the production of polypeptides comprising one or more unnatural amino acids. Further provided are cells, engineered microorganisms, and kits for increasing the retention of unnatural nucleic acids encoding the unnatural amino acids in an engineered cell, or semi-synthetic organism.

Unnatural base pair compositions and methods of use

Disclosed herein are compositions, methods, cells, engineered microorganisms, and kits for increasing the production of proteins or polypeptides comprising one or more unnatural amino acids. Further provided are compositions, cells, engineered microorganisms, and kits for increasing the retention of unnatural nucleic acids encoding the unnatural amino acids in an engineered cell, or semi-synthetic organism.

Reagents and methods for replication, transcription, and translation in semi-synthetic organisms

Disclosed herein are proteins, methods, cells, engineered microorganisms, and kits for generating a modified nucleoside triphosphate transporter from. Also disclosed herein proteins, methods, cells, engineered microorganisms, and kits for production of a nucleic acid molecule that comprises an unnatural nucleotide utilizing a modified nucleoside triphosphate transporter from

Nucleoside triphosphate transporter and uses thereof

Disclosed herein are methods, cells, engineered microorganisms, and kits for increased production of a nucleic acid molecule that comprises an unnatural nucleotide.

Production of unnatural nucleotides using a CRISPR/Cas9 system

A recombinantly expressed nucleotide triphosphate transporter efficiently imports the triphosphates of unnatural nucleotides into cells, and the endogenous cellular machinery incorporates those nucleotides into cellular nucleic acids. UBPs can therefore form within the cell's nucleic acids. Moreover, neither the presence of the unnatural triphosphates nor the replication of the UBP represents a significant growth burden. The UBP is not efficiently excised by nucleic acid repair pathways, and therefore can be retained as long as the unnatural triphosphates are available in the growth medium. Thus, the resulting cell is the first organism to stably propagate an expanded genetic alphabet.

Import of unnatural or modified nucleoside triphosphates into cells via nucleic acid triphosphate transporters

Arylomycin analogs are provided, wherein the analogs can have broad spectrum bioactivity. Resistance to the antibiotic bioactivity of natural product arylomycin in a range of pathogenic bacterial species has been found to depend upon single amino acid mutations at defined positions of bacterial Signal Peptidases (SPases), wherein the presence of a proline residue confers arylomycin resistance. Arylomycin analogs are provided herein that can overcome that resistance and provide for a broader spectrum of antibiotic bioactivity than can natural product arylomycins such as arylomycin A2. Methods for determining if a bacterial strain is susceptible to narrow spectrum arylomycin antibiotics, or if a broad spectrum analog is required for treatment, is provided. Pharmaceutical compositions and methods of treatment of bacterial infections, and methods of synthesis of arylomycin analogs, are provided.

Broad spectrum antibiotic arylomycin analogs

The present invention provides methods and compositions for said inhibition of drug resistance. In one embodiment, said invention provides methods and compositions for said inhibition of antibiotic resistance. The invention generally involves said administration of achaogens, agents that inhibit said mutational process, to inhibit said evolution of drug resistance. Also, described herein are compositions that are suitable for use as achaogens.

Compositions and methods to reduce mutagenesis

Growing community of inventors

La Jolla, CA, United States of America

Floyd E Romesberg