Harvard College

The General Hospital Corporation

Other

Dana-farber-cancer Institute Inc.

John J Mekalanos

Samuel I Miller, Iii

Andrew Camilli

Ronald K Taylor

R John Collier

Stephen B Calderwood

Marek Basler

Eric J Rubin

Samuel I Miller

Brian J Akerley

Kevin Killeen

Philip J Kranzusch

Matthew K Waldor

Karl E Klose

Aaron T Whiteley

Claudette L Gardel

Wen Zhou

James M Slauch

Michael J Mahan

Joan R Butterton

The present invention is based, in part, on the discovery of the human-specific regulatory control of cGAS and the structure of the active human cGAS-DNA complex, as well as compositions comprising the modified hcGAS polypeptide, hcGAS-DNA complex, hcGAS-DNA-ATP complex, and methods of screening for modulators of the structure, expression, and/or activity of such polypeptides and complexes.

Human CGAS-DNA complex and encoded protein

Provided herein are methods and compositions for displaying a polypeptide on a tubular structure and uses of such displayed polypeptides in the production of antibodies or vaccines.

Methods for displaying polypeptides and uses thereof

The invention relates to vaccine compositions having a carrier protein and an antigen of interest entrapped in a complex, methods of making such vaccines, and methods of vaccine administration.

Protein matrix vaccines and related methods of making and administering such vaccines

Protein matrix vaccines and methods of making and administering such vaccines

A live non-virulent vaccine composition and method for preparing the same comprising a virulent microorganismal strain which contains at least two mutations, wherein the first mutation results in an auxotrophic mutant which requires for proliferation, a nutrient which is normally available in the host tissues in an amount required by the auxotrophic mutant for proliferation and the second mutation results in the inability of the auxotrophic mutant to specifically transport the required nutrient from host-tissues into the auxotrophic mutant thereby producing an attenuated strain.

Attenuated auxotrophic microorganisms having a combination of non-attenuating mutations and method for making same

The invention features a general system for the identification of essential genes in organisms. This system is applicable to the discovery of novel target genes for antimicrobial compounds, as well as to the discovery of genes that enhance cell growth or viability.

Systematic identification of essential genes by in vitro transposon mutagenesis

vaccine strains which have a soft agar penetration-defective phenotype and methods for making such strains are described. Also described are methods for identifying new genes involved in,motility and the cloning, identification, and sequencing of,motB and fliC genes.

Vibrio cholerae mutants which are soft-agar penetration defective and lack a functional CtxA subunit

A vector capable of integrating into the chromosome of Salmonella including a first DNA sequence encoding a heterologous protein, a second DNA sequence encoding a marker, and a third DNA sequence encoding a phoP regulatory region regulated gene product necessary for virulence, the third DNA sequence being mutationally inactivated.

Salmonella virulence genes

The invention provides bacterial strains with increased sensitivity to antibiotics and methods for making and using the strains.

Vibrio cholerae having increased sensitivity to antibiotics

Deletion mutants of cholera vaccines expressing heterologous antigens

The invention features a Salmonella cell the virulence of which is attenuated by a deletion of a portion of the PhoQ gene and Salmonella cells having a deletion of the PhoQ gene and a deletion of the PhoP gene. The invention also features vaccines comprising such bacteria.

Salmonella vaccines

A bacterial cell (preferably a gram-negative, enteric bacterium such as V. cholerae) the chromosome of which which contains a DNA sequence encoding a heterologous antigen, which sequence is functionally linked to an iron-regulated promoter such as the irgA promoter of V. cholerae.

Immunizing compositions comprising Vibrio cholerae expressing

A vector capable of integrating into the chromosome of Salmonella including a first DNA sequence encoding a heterologous protein, a second DNA sequence encoding a marker, and a third DNA sequence encoding a phoP regulatory region regulated gene product necessary for virulence, the third DNA sequence being mutationally inactivated

A bacterial cell the virulence of which is attentuated by a first mutation in a PhoP regulon and a second mutation in an aromatic amino acid synthetic gene and bacterial cells the virulence of which is attenuated by a mutation in one or more PhoP-activated genes or one or more PhoP-repressed genes.

Growing community of inventors

Cambridge, MA, United States of America

John J Mekalanos