Dana-farber-cancer Institute Inc.

Alnylam Pharmaceuticals, Inc.

William G Kaelin

Mircea Ivan

David M Livingston

Brian R Bettencourt

William Querbes

Victor E Kotelianski

William R Sellers

Christine Jost

Erik Flemington

Tae-You Kim

James A DeCaprio

Vidyasagar Koduri

The present application relates, in some aspects, to the development of an assay that uses cell survival and/or cell viability as a phenotypic identifier to positively select for agents that destabilize a protein of interest.

Methods and compositions for the positive selection of protein destabilizers

Light-generating fusion proteins having a ligand binding site and a light-generating polypeptide moiety and their use as diagnostics, in drug screening and discovery, and as therapeutics, are disclosed. The light-generating fusion protein has a feature where the bioluminescence of the polypeptide moiety changes upon binding of a ligand at the ligand binding site. The ligand may be, for example, an enzyme present in an environment only under certain conditions, e.g., ubiquitin ligase in a hypoxic state, such that the light-generating fusion protein is 'turned on' only under such conditions.

Pharmaceuticals and methods for treating hypoxia and screening methods therefor

The invention relates to double-stranded ribonucleic acid (dsRNA) compositions targeting one or more EGLN genes, EGLN1, EGLN2 and/or EGLN3 and methods of using such dsRNA compositions to inhibit expression of these genes.

Compositions and methods for increasing erythropoietin (EPO) production

Method of identifying a compound for treating a hypoxic or ischemic related disorder

The present invention provides methods of identifying compounds that decrease proline hydroxylation of the alpha subunit of hypoxia inducible factor (HIF&#x3b1;).

HIF&#x3b1; hydroxylation assay

HIF&#x3b1;prolyl hydroxylation assay

Light-emitting fusion proteins and diagnostic and therapeutic methods therefor

Antibodies that will specifically bind to NBS-1 are described. It is also shown that NBS-1 will interact with p53 responsive elements in a p53 promoter. Thus, NBS-1 can be used in subjects having a p53-dependent tumor to inhibit growth of that tumor.

Methods of treatment using NBS-1, antibodies and proteins thereto, and uses of the antibodies

The present invention provides hypoxia inducible factor alpha muteins, DNA sequences encoding these hypoxia inducible factor alpha muteins, recombinant DNA molecules containing those DNA sequences operatively linked to expression control sequences and capable of inducing expression of an hypoxia inducible factor alpha muteins, hosts transformed with those recombinant DNA molecules, pharmaceutical compositions containing hypoxia inducible factor alpha muteins and methods of using those compositions to treat hypoxia and ischemic related tissue damage.

Muteins of hypoxia inducible factor alpha and methods of use thereof

Transgenic animals expressing light-emitting fusion proteins and diagnostic and therapeutic methods therefor

Light-generating fusion proteins having a ligand binding site and a light-generating polypeptide moiety and their use as diagnostics, in drug screening and discovery, and as therapeutics, are disclosed. The light-generating fusion protein has a feature where the bioluminescence of the polypeptide moiety changes upon binding of a ligand at the ligand binding site. Tie ligand may be, for example, an enzyme present in an environment only under certain conditions, e.g., ubiquitin ligase in a hypoxic state, such that the light-generating fusion protein is 'turned on' only under such conditions.

We have discovered a nuclear protein in normal human cells, 'retinoblastoma-associated protein 1' ('RBAP-1') that binds directly to the retinoblastoma protein pocket of the underphosphorylated form of the retinoblastoma protein ('RB') and does not bind to phosphorylated RB or to RB with inactivating mutations. The translated RBAP-1 sequence does not resemble other proteins whose sequences are known, and RBAP-1 does not contain a sequence homologous to the transforming element common to viral proteins that bind to the RB pocket. RBAP-1 and the E2F transcription activity have similar DNA-binding specificities and can bind to at least some of the same proteins, such as RB and E4.

Growing community of inventors

Boston, MA, United States of America

William G Kaelin