Published online Dec 26, 2015. doi: 10.4252/wjsc.v7.i11.1233
Peer-review started: August 8, 2015
First decision: September 22, 2015
Revised: October 8, 2015
Accepted: November 23, 2015
Article in press: November 25, 2015
Published online: December 26, 2015
With the advent of safer and more efficient gene transfer methods, gene therapy has become a viable solution for many inherited and acquired disorders. Hematopoietic stem cells (HSCs) are a prime cell compartment for gene therapy aimed at correcting blood-based disorders, as well as those amenable to metabolic outcomes that can effect cross-correction. While some resounding clinical successes have recently been demonstrated, ample room remains to increase the therapeutic output from HSC-directed gene therapy. In vivo amplification of therapeutic cells is one avenue to achieve enhanced gene product delivery. To date, attempts have been made to provide HSCs with resistance to cytotoxic drugs, to include drug-inducible growth modules specific to HSCs, and to increase the engraftment potential of transduced HSCs. This review aims to summarize amplification strategies that have been developed and tested and to discuss their advantages along with barriers faced towards their clinical adaptation. In addition, next-generation strategies to circumvent current limitations of specific amplification schemas are discussed.
Core tip: Though hematopoietic stem cell (HSC)-directed gene therapy is becoming a viable therapy for many disorders, optimization of clinical output needs improvement. One approach to circumvent lower efficiencies of gene transfer and/or engraftment is to apply in vivo amplification strategies. Here we review various modules that have been developed and tested to mediate amplification of HSCs after gene transfer.