Faculty Collaboration Database

Megakaryocyte- and megakaryocyte precursor-related gene therapies. Blood 2016 Mar 10;127(10):1260-8

Date

01/21/2016

Pubmed ID

26787735

Pubmed Central ID

PMC4786835

DOI

10.1182/blood-2015-07-607937

Scopus ID

2-s2.0-84960889147 (requires institutional sign-in at Scopus site)   16 Citations

Abstract

Hematopoietic stem cells (HSCs) can be safely collected from the body, genetically modified, and re-infused into a patient with the goal to express the transgene product for an individual's lifetime. Hematologic defects that can be corrected with an allogeneic bone marrow transplant can theoretically also be treated with gene replacement therapy. Because some genetic disorders affect distinct cell lineages, researchers are utilizing HSC gene transfer techniques using lineage-specific endogenous gene promoters to confine transgene expression to individual cell types (eg, ITGA2B for inherited platelet defects). HSCs appear to be an ideal target for platelet gene therapy because they can differentiate into megakaryocytes which are capable of forming several thousand anucleate platelets that circulate within blood vessels to establish hemostasis by repairing vascular injury. Platelets play an essential role in other biological processes (immune response, angiogenesis) as well as diseased states (atherosclerosis, cancer, thrombosis). Thus, recent advances in genetic manipulation of megakaryocytes could lead to new and improved therapies for treating a variety of disorders. In summary, genetic manipulation of megakaryocytes has progressed to the point where clinically relevant strategies are being developed for human trials for genetic disorders affecting platelets. Nevertheless, challenges still need to be overcome to perfect this field; therefore, strategies to increase the safety and benefit of megakaryocyte gene therapy will be discussed.

Author List

Wilcox DA

Author

David A. Wilcox PhD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Genetic Therapy
Hematologic Diseases
Hematopoietic Stem Cell Transplantation
Humans
Integrin alpha2
Megakaryocyte Progenitor Cells
Megakaryocytes
Transgenes