Targeted heat shock protein 72 for pulmonary cytoprotection

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Abstract

Heat shock protein 72 (HSP72) is perhaps the most important member of the HSP70 family of proteins, given that it is induced in a wide variety of tissues and cells to combat stress, particularly oxidative stress. Here, we review independent observations of the critical role this protein plays as a pulmonary cytoprotectant and discuss the merits of developing HSP72 as a therapeutic for rapid delivery to cells and tissues after a traumatic event. We also discuss the fusion of HSP72 to a cell-penetrating single-chain Fv antibody fragment derived from mAb 3E10, referred to as Fv–HSP70. This fusion construct has been validatedin vivoin a cerebral infarction model and is currently in testing as a clinical therapeutic to treat ischemic events and as a fieldable medical countermeasure to treat inhalation of toxicants caused by terrorist actions or industrial accidents.

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