Issues in the manufacture and transplantation of... : Current Opinion in Hematology (original) (raw)

Hematopoietic stem cell transplantation

Issues in the manufacture and transplantation of genetically modified hematopoietic stem cells

Sadelain, Michel MD, PhD*; Frassoni, Francesco MD†; Rivière, Isabelle PhD*

*Gene Transfer and Somatic Cell Engineering Facility, Department of Human Genetics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA; †Department of Hematology, San Martino Hospital, Genova, Italy

Correspondence to Michel Sadelain, MD, PhD, Memorial Sloan-Kettering Cancer Center, Box 182, 1275 York Avenue, New York, NY 10021, USA; e-mail: [email protected]

Abstract

The advent of safe and practical means to correct, enhance or protect blood cells at the genetic level offers tantalizing therapeutic perspectives. At present, gene delivery using a replication-defective retrovirus is the most efficient method to stably transduce hematopoietic cells. The successful adaptation of retroviral infection to hematopoietic stem cells requires optimized transduction conditions that maximize gene transfer while preserving the cells’ potential for engraftment and long-term hematopoiesis. The successful establishment of effective transduction protocols hinges on retrovirus biology as well as stem cell and transplantation biology. Interestingly, the genetic approach could permit novel strategies to promote host repopulation by transplanted stem cells. However, regulated and predictable expression of any transgene integrated at random chromosomal locations cannot be taken for granted. Investigation of the control of transgene expression and prevention of vector silencing will become increasingly important.