ReviewDelivery of RNA-based molecules to human hematopoietic stem and progenitor cells for modulation of gene expression

•Primary hematopoietic stem and progenitor cells (HSPCs) are notoriously difficult to transfect, particularly with chemical methods.•Electroporation is the method of choice for nonviral modulation of HSPCs.•Different types of RNA molecules allow protein overexpression as well as downregulation in HSPCs.•The decreased stability of RNA compared with DNA enables improved temporal control of expression.

Gene modulation of human hematopoietic stem and progenitor cells (HSPCs) harbors great potential for therapeutic application of these cells and presents a versatile tool in basic research to enhance our understanding of HSPC biology. However, stable genetic modification might be adverse, particularly in clinical settings. Here, we review a broad range of approaches to transient, nonviral modulation of protein expression with a focus on RNA-based methods. We compare different delivery methods and describe the usefulness of RNA molecules for overexpression as well as downregulation of proteins in HSPCs.