Massachusetts Institute of Technology

Merck + Co., Inc.

Stefanie A Kane

Stephen J Lippard

Christopher A Salvatore

Kenneth S Koblan

John J Mallee

Kevin R Oliver

Disclosed herein are isolated nucleic acid molecules encoding a humanized version of a calcitonin gene-related peptide (CGRP) receptor, which comprises the G-protein coupled receptor calcitonin-receptor-like receptor (CRLR) and the receptor-activity-modifying protein 1 (RAMP1). The humanized CGRP receptors of the present invention attain pharmacological profiles similar to the wild type human receptor via modifications to the respective mammalian RAMP1 nucleotide sequence, specifically at amino acid 74. Also described are related recombinant vectors, recombinant hosts and associated methods for generating such humanized CGRP receptors. Also presented are non-human transgenic animals which express humanized RAMP1. Such animals have been engineered to provide for a CGRP pharmacological profile similar to human CGRP.

Isolated DNA molecules encoding humanized calcitonin gene-related peptide receptor, related non-human transgenic animals and assay methods

Methods disclosed herein capitalize on the discovery that DNA Structure Specific Recognition Proteins (SSRPs) can be induced to bind covalently to genomic lesions formed by chemotherapeutic agents, particularly cisplatin-type agents, by photo-irradiation with ultraviolet light. Methods and compositions based on this discovery are provided for sensitizing particular eukaryotic cells to killing by chemotherapeutic agents, particularly cisplatin-type drugs. Methods and compositions also are provided for potentiating cytotoxicity of a chemotherapeutic agent, particularly a cisplatin-type agent.

Photo-potentiation of cisplatin chemotherapy

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Schwenksville, PA, United States of America

Stefanie A Kane