Project Grant R61HL163739

This Project Grant from the National Heart, Lung and Blood Institute, part of the Department of Health and Human Services, provides $914,900 to Ship Of Theseus LLC under the Cardiovascular Diseases Research program (CFDA 93.837). The funding supports preclinical development of a nuclear-targeting biologic to safely increase stem cell expansion in vivo and accelerate recovery from neutropenia following chemotherapy and bone marrow transplant.

Specifically, the grant will advance a patented mutant of the nuclear transcription factor HOXB4 (HOXB4(M)) that promotes hematopoietic stem cell expansion without differentiation. The goals are to improve HOXB4(M)'s nuclear delivery efficiency and safety by identifying optimal combinations of cell penetrating peptides and nuclear localization motifs. In vitro and in vivo studies in mice will assess top candidates to select a lead biologic demonstrating long-term hematopoietic reconstitution without adverse effects. Successful completion will provide data to support future efficacy and safety studies necessary for an investigational new drug application. The technology aims to shorten the risky neutropenic phase after transplants and reduce costs by circumventing limitations of ex vivo culturing methods.