In Vivo Hematopoietic Stem Cell Transduction

Maximilian Richter; Daniel Stone; Carol Miao; Olivier Humbert; Hans-Peter Kiem; Thalia Papayannopoulou; André Lieber

doi:10.1016/j.hoc.2017.06.001

In Vivo Hematopoietic Stem Cell Transduction

Hematol Oncol Clin North Am. 2017 Oct;31(5):771-785. doi: 10.1016/j.hoc.2017.06.001.

Authors

Maximilian Richter¹, Daniel Stone², Carol Miao³, Olivier Humbert⁴, Hans-Peter Kiem⁵, Thalia Papayannopoulou⁶, André Lieber⁷

Affiliations

¹ Division of Medical Genetics, University of Washington, 1705 NE Pacific Street, Seattle, WA 98195, USA.
² Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, Seattle, WA 98109, USA.
³ Department of Pediatrics, University of Washington, 1705 NE Pacific Street, Seattle, WA 98195, USA; Center for Immunity and Immunotherapy, Research Institute, Seattle Children's Hospital, 1900 9th Avenue, Seattle, WA 98101, USA.
⁴ Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Aveune N, Seattle, WA 98109, USA.
⁵ Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Aveune N, Seattle, WA 98109, USA; Department of Medicine, University of Washington School of Medicine, 1705 NE Pacific Street, Seattle, WA 98195, USA.
⁶ Division of Hematology, University of Washington, 1705 NE Pacific Street, Seattle, WA 98195, USA.
⁷ Division of Medical Genetics, University of Washington, 1705 NE Pacific Street, Seattle, WA 98195, USA; Department of Pathology, University of Washington, 1705 NE Pacific Street, Seattle, WA 98195, USA. Electronic address: lieber00@uw.edu.

Abstract

Current protocols for hematopoietic stem cell (HSC) gene therapy, involving the transplantation of ex vivo lentivirus vector-transduced HSCs into myeloablated recipients, are complex and not without risk for the patient. In vivo HSC gene therapy can be achieved by the direct modification of HSCs in the bone marrow after intraosseous injection of gene delivery vectors. A recently developed approach involves the mobilization of HSCs from the bone marrow into peripheral the blood circulation, intravenous vector injection, and re-engraftment of genetically modified HSCs in the bone marrow. We provide examples for in vivo HSC gene therapy and discuss advantages and disadvantages.

Keywords: Intraosseal; Intravenous; Mobilization; Viral vectors.

Publication types

Review

MeSH terms

Animals
Bone Marrow Cells / cytology
Bone Marrow Cells / metabolism
Gene Editing
Gene Expression
Gene Transfer Techniques
Genetic Therapy* / methods
Genetic Vectors / administration & dosage
Genetic Vectors / classification
Genetic Vectors / genetics*
Hematopoietic Stem Cell Mobilization / methods
Hematopoietic Stem Cells / cytology
Hematopoietic Stem Cells / metabolism*
Humans
Transduction, Genetic*
Transgenes

Abstract

Publication types

MeSH terms

Grants and funding